35 results on '"Hanna Vauhkonen"'
Search Results
2. Introduction and Rapid Spread of SARS-CoV-2 Omicron Variant and Dynamics of BA.1 and BA.1.1 Sublineages, Finland, December 2021
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Hanna Vauhkonen, Phuoc Truong Nguyen, Ravi Kant, Ilja Plyusnin, Mert Erdin, Satu Kurkela, Hanna Liimatainen, Niina Ikonen, Soile Blomqvist, Kirsi Liitsola, Erika Lindh, Otto Helve, Hanna Jarva, Raisa Loginov, Aino Palva, Tiina Hannunen, Sari Hannula, Mikko Parry, Paula Kauppi, Antti Vaheri, Tarja Sironen, Maija Lappalainen, Carita Savolainen-Kopra, Teemu Smura, and Olli Vapalahti
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COVID-19 ,SARS-CoV-2 ,SARS-CoV-2 Omicron variant ,SARS-CoV-2 Omicron sublineages BA.1 and BA.1.1 ,disease spread ,Finland ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
Multiple introductions of SARS-COV-2 Omicron variant BA.1 and BA.1.1. lineages to Finland were detected in early December 2021. Within 3 weeks, Omicron overtook Delta as the most common variant in the capital region. Sequence analysis demonstrated the emergence and spread through community transmission of a large cluster of BA.1.1 virus.
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- 2022
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3. Puumala Hantavirus Infections Show Extensive Variation in Clinical Outcome
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Antti Vaheri, Teemu Smura, Hanna Vauhkonen, Jussi Hepojoki, Tarja Sironen, Tomas Strandin, Johanna Tietäväinen, Tuula Outinen, Satu Mäkelä, Ilkka Pörsti, and Jukka Mustonen
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orthohantavirus ,hemorrhagic fever with renal syndrome ,HLA ,nephropathia epidemica ,Puumala hantavirus ,biomarker ,Microbiology ,QR1-502 - Abstract
The clinical outcome of Puumala hantavirus (PUUV) infection shows extensive variation, ranging from inapparent subclinical infection (70–80%) to severe hemorrhagic fever with renal syndrome (HFRS), with about 0.1% of cases being fatal. Most hospitalized patients experience acute kidney injury (AKI), histologically known as acute hemorrhagic tubulointerstitial nephritis. Why this variation? There is no evidence that there would be more virulent and less virulent variants infecting humans, although this has not been extensively studied. Individuals with the human leukocyte antigen (HLA) alleles B*08 and DRB1*0301 are likely to have a severe form of the PUUV infection, and those with B*27 are likely to have a benign clinical course. Other genetic factors, related to the tumor necrosis factor (TNF) gene and the C4A component of the complement system, may be involved. Various autoimmune phenomena and Epstein-Barr virus infection are associated with PUUV infection, but hantavirus-neutralizing antibodies are not associated with lower disease severity in PUUV HFRS. Wide individual differences occur in ocular and central nervous system (CNS) manifestations and in the long-term consequences of nephropathia epidemica (NE). Numerous biomarkers have been detected, and some are clinically used to assess and predict the severity of PUUV infection. A new addition is the plasma glucose concentration associated with the severity of both capillary leakage, thrombocytopenia, inflammation, and AKI in PUUV infection. Our question, “Why this variation?” remains largely unanswered.
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- 2023
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4. Intrinsic structural variation of the complex microsatellite marker MYCL1 in Finnish and Somali populations and its relevance to gastrointestinal tumors
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Hanna Vauhkonen and Antti Sajantila
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colorectal cancers ,complex microsatellite ,gastrointestinal tumors ,microsatellite instability ,Finnish and Somali populations ,Genetics ,QH426-470 - Abstract
The structurally complex MYCL1 microsatellite marker is often used to determine microsatellite instability in colorectal cancers but the allelic variation of this marker has remained largely uncharacterized in both populations and in cancers. Our study describes the allelic distributions of MYCL1 in Finnish (n = 117) and Somali population samples (n = 61) of non-related individuals and compares this distribution with the instability pattern obtained from 61 gastrointestinal tumors.
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- 2006
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5. Copy number analysis of complement C4A, C4B and C4A silencing mutation by real-time quantitative polymerase chain reaction.
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Riitta Paakkanen, Hanna Vauhkonen, Katja T Eronen, Asko Järvinen, Mikko Seppänen, and Marja-Liisa Lokki
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Medicine ,Science - Abstract
Low protein levels and copy number variation (CNV) of the fourth component of human complement (C4A and C4B) have been associated with various diseases. High-throughput methods for analysing C4 CNV are available, but they commonly do not detect the most common C4A mutation, a silencing CT insertion (CTins) leading to low protein levels. We developed a SYBR® Green labelled real-time quantitative polymerase chain reaction (qPCR) with a novel concentration range approach to address C4 CNV and deficiencies due to CTins. This method was validated in three sample sets and applied to over 1600 patient samples. CTins caused C4A deficiency in more than 70% (76/105) of the carriers. Twenty per cent (76/381) of patients with a C4A deficiency would have been erroneously recorded as having none, if the CTins had not been assessed. C4A deficiency was more common in patients than a healthy reference population, (OR = 1.60, 95%CI = 1.02-2.52, p = 0.039). The number of functional C4 genes can be straightforwardly analyzed by real-time qPCR, also with SYBR® Green labelling. Determination of CTins increases the frequency of C4A deficiency and thus helps to elucidate the genotypic versus phenotypic disease associations.
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- 2012
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6. Correction: Copy Number Analysis of Complement , and Silencing Mutation by Real-Time Quantitative Polymerase Chain Reaction.
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Riitta Paakkanen, Hanna Vauhkonen, Katja T. Eronen, Asko Järvinen, Mikko Seppänen, and Marja-Liisa Lokki
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Medicine ,Science - Published
- 2012
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7. Single nucleotide polymorphism microarray analysis of karyotypically normal acute myeloid leukemia reveals frequent copy number neutral loss of heterozygosity
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Anne Tyybäkinoja, Erkki Elonen, Hanna Vauhkonen, Janna Saarela, and Sakari Knuutila
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2008
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8. Intrahost variation in early monkeypox virus cases introduced to Finland, 2022
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Hanna Vauhkonen, Hannimari Kallio-Kokko, Eija Hiltunen-Back, Lasse Lönnqvist, Jaana Leppäaho-Lakka, Laura Mannonen, Ravi Kant, Tarja Sironen, Satu Kurkela, Maija Lappalainen, Tomaž Mark Zorec, Samo Zakotnik, Doroteja Vlaj, Miša Korva, Tatjana Avšič-Županc, Mario Poljak, Teemu Smura, and Olli Vapalahti
- Abstract
We report early importations of monkeypox virus to Finland during late May - early June 2022. Intrahost viral genome variation in one sample comprised a major variant with three lineage B.1.3-specific mutations and a minor variant with ancestral B.1 nucleotides, suggesting either ongoing APOBEC3-mediated evolution or coinfection.
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- 2022
9. Genomic and epidemiological report of the recombinant XJ lineage SARS-CoV-2 variant, detected in northern Finland, January 2022
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Erika Lindh, Teemu Smura, Soile Blomqvist, Kirsi Liitsola, Hanna Vauhkonen, Laura Savolainen, Jaana Ikonen, Jukka Ronkainen, Jyri Taskila, Tea Taskila, Pertti Sakaranaho, Carita Savolainen-Kopra, Olli Vapalahti, Niina Ikonen, Department of Virology, HUSLAB, Veterinary Biosciences, Veterinary Microbiology and Epidemiology, Helsinki One Health (HOH), and Viral Zoonosis Research Unit
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SARS-CoV-2 ,Epidemiology ,Virology ,Public Health, Environmental and Occupational Health ,COVID-19 ,Humans ,Genomics ,3111 Biomedicine ,Finland - Abstract
Recombinant sequences of the SARS-CoV-2 Omicron variant were detected in surveillance samples collected in north-western Finland in January 2022. We detected 191 samples with an identical genome arrangement in weeks 3 to 11, indicating sustained community transmission. The recombinant lineage has a 5’-end of BA.1, a recombination breakpoint between orf1a and orf1b (nucleotide position 13,296–15,240) and a 3’-end of BA.2 including the S gene. We describe the available genomic and epidemiological data about this currently circulating recombinant XJ lineage.
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- 2022
10. Introduction and rapid spread of SARS-CoV-2 Omicron variant and the dynamics of its sub-lineages BA.1 and BA.1.1, December 2021, Finland
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Hanna Vauhkonen, Phuoc Truong, Ravi Kant, Ilja Plyusnin, Mert Erdin, Satu Kurkela, Hanna Liimatainen, Niina Ikonen, Soile Blomqvist, Kiirsi Liitsola, Erika Lindh, Otto Helve, Hanna Jarva, Raisa Longinov, Aino Palva, Tiina Hannunen, Sari Hannula, Mikko Parry, Paula Kauppi, Antti Vaheri, Tarja Sironen, Maija Lappalainen, Carita Savolainen-Kopra, Teemu Smura, and Olli Vapalahti
- Abstract
Multiple introductions of SARS-COV-2 Omicron variant BA.1. and BA.1.1. lineages to Finland were detected early December 2021, and comprised the majority over Delta variant in 3 weeks in the capital region. Our sequence analysis demonstrates emergence of a large cluster of BA.1.1 in community transmission.
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- 2022
11. Gene copy number analysis in malignant pleural mesothelioma using oligonucleotide array CGH
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Pamela Lindholm, Hanna Vauhkonen, A G Nicholson, Sisko Anttila, Vuokko L. Kinnula, Sakari Knuutila, and Kaisa Salmenkivi
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Mesothelioma ,Genome, Human ,Pleural Neoplasms ,Gene Dosage ,Nucleic Acid Hybridization ,Locus (genetics) ,Biology ,medicine.disease_cause ,Molecular biology ,Genome ,Nucleic acid thermodynamics ,CDKN2A ,CDKN2B ,Genetics ,medicine ,Humans ,Copy-number variation ,Carcinogenesis ,Molecular Biology ,Genetics (clinical) ,Oligonucleotide Array Sequence Analysis ,Comparative genomic hybridization - Abstract
Conventional cytogenetic analyses and comparative genomic hybridization have revealed a complex and even chaotic nature of chromosomal aberrations in pleural malignant mesothelioma (MM). We set out to describe the complex gene copy number changes and screen for novel genetic aberrations using a high-density oligonucleotide microarray platform for comparative genomic hybridization (aCGH) of a series of 26 well-characterized MM tumor samples. The number of copy number changes varied from zero to 40 per sample. Gene copy number losses predominated over gains, and the most frequent region of loss was 9p21.3 (17/26 cases), the locus of CDKN2A and CDKN2B, both known to be commonly lost in MM. The most recurrent minimal regions of losses were 1p31.1→ p13.2, 3p22.1→p14.2, 6q22.1, 9p21.3, 13cen→q14.12, 14q22.1→qter, and 22qcen→q12.3. Previously unreported gains included 9p13.3, 7p22.3→p22.2, 12q13.3, and 17q21.32→qter. The results suggest that gene copy number losses are a major mechanism of MM carcinogenesis and reveal a recurrent pattern of copy number changes in MM.
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- 2007
12. Loss of TP53 in sarcomas with 17p12~p11 gain. A fine-resolution oligonucleotide array comparative genomic hybridization study
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Sippy Kaur, Sakari Knuutila, Hanna Vauhkonen, Marcelo L. Larramendy, and Tom Böhling
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Leiomyosarcoma ,Locus (genetics) ,Biology ,medicine.disease ,Gene dosage ,Molecular biology ,Chromosome 17 (human) ,Genetics ,medicine ,Osteosarcoma ,Sarcoma ,Molecular Biology ,Genetics (clinical) ,Virtual karyotype ,Comparative genomic hybridization - Abstract
The amplification or gain of the p-arm of chromosome 17 is common in sarcomas, suggesting its role in carcinogenesis. Here, we report the architectural structure and targets of 17p aberrations commonly shared by osteosarcoma (OS), leiomyosarcoma (LMS) and malignant fibrous histiocytoma (MFH) of soft tissue. Two low-grade and two high-grade soft tissue LMS, three OS, and two MFH samples were studied using fine-resolution oligonucleotide-based microarray comparative genomic hybridization. Eight of the nine samples showed a loss of 17pter→p13, the locus of tumor suppressor TP53 preceding the amplified area 17p12→p11.2. The size and detailed architecture of the amplified region of 17p differed between the studied sarcoma entities. OS and high-grade LMS showed similar complex patterns of discontinuous amplifications with regions of gain in between. MFH and low-grade LMS showed continuous regions of gains and amplifications. Precise boundaries of the lost or gained regions were determined, and in addition to the previously suggested targets of the region, ELAC and FLCN were amplified in all the sarcoma entities.
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- 2007
13. Oligonucleotide array comparative genomic hybridization refines the structure of 8p23.1, 17q12 and 20q13.2 amplifications in gastric carcinomas
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Matti Vauhkonen, Sakari Knuutila, Hanna Vauhkonen, and P. Sipponen
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Chromosomes, Human, Pair 20 ,Gene Dosage ,Biology ,DNA Copy Number Changes ,03 medical and health sciences ,0302 clinical medicine ,Stomach Neoplasms ,Genetics ,medicine ,Humans ,Copy-number variation ,skin and connective tissue diseases ,Molecular Biology ,Genetics (clinical) ,Aged ,Oligonucleotide Array Sequence Analysis ,030304 developmental biology ,Aged, 80 and over ,0303 health sciences ,Oligonucleotide ,Gene Amplification ,Nucleic Acid Hybridization ,Cancer ,Middle Aged ,medicine.disease ,Molecular biology ,stomatognathic diseases ,Phenotype ,030220 oncology & carcinogenesis ,sense organs ,Virtual karyotype ,Chromosomes, Human, Pair 17 ,Chromosomes, Human, Pair 8 ,Comparative genomic hybridization ,SNP array - Abstract
Oligonucleotide array comparative genomic hybridization (aCGH) was applied on fifteen gastric cancer (GCA) samples to reveal information of DNA copy number changes at an exon-level resolution. Twelve of the samples represented the intestinal (IGCA) and three the diffuse (DGCA) type of GCA. The samples had previously been assessed for genetic stability by microsatellite analysis and categorized into microsatellite phenotypes according to the type of alterations. As compared to our previous results obtained using cDNA platforms, the oligonucleotide platforms revealed more aberrations per sample (0–45 vs. 0–22). A total of 22 amplifications were detected by the oligonucleotide arrays. Ten of the amplicons had also been detected on the cDNA platform, but five of them spanned only one or a few cDNA clones, thus resembling apparent outliers. Two tumors showed five or more amplifications by oligonucleotide aCGH, suggesting the presence of an amplifier phenotype. The amplifications occurred irrespective of the microsatellite phenotypes. None of the DGCA tumors showed more than one aberration, whereas the IGCA tumors showed several aberrations. The increased resolution of the oligonucleotide arrays enabled the detection of amplicon boundaries at gene level, allowing, e.g., the determination of the 17q12 core amplicon and interstitial losses within the 8p23.1→p22 and 20q13.2→q13.1 amplifications. Previously no losses have been reported within amplified regions in GCA. In addition to novel amplified regions, the oligonucleotide array results describe novel targets for amplicons at 8p11 (SFRP1), 11p12 (LRRC4C), and 19q13.2 (CEACAM6).
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- 2007
14. Characterizing genetically stable and unstable gastric cancers by microsatellites and array comparative genomic hybridization
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Antti Sajantila, Sakari Knuutila, Matti Vauhkonen, Pentti Sipponen, and Hanna Vauhkonen
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Male ,Cancer Research ,Gene Dosage ,Loss of Heterozygosity ,Biology ,Genomic Instability ,Loss of heterozygosity ,03 medical and health sciences ,0302 clinical medicine ,Stomach Neoplasms ,Complementary DNA ,Genetics ,medicine ,Humans ,neoplasms ,Molecular Biology ,Aged ,Oligonucleotide Array Sequence Analysis ,030304 developmental biology ,Aged, 80 and over ,0303 health sciences ,Nucleic Acid Hybridization ,Microsatellite instability ,Cancer ,Middle Aged ,Amplicon ,medicine.disease ,Molecular biology ,digestive system diseases ,030220 oncology & carcinogenesis ,Microsatellite ,Female ,Microsatellite Instability ,Virtual karyotype ,Comparative genomic hybridization - Abstract
Gastric cancer (GCA) displays a variety of genomic aberrations, including DNA copy number alterations, microsatellite instability (MSI), and loss of heterozygosity (LOH). The main aim of the present work was to determine the copy number aberrations in tumors with and without MSI or LOH. Fifteen fresh-frozen GCA samples, 11 of the intestinal and 4 of the diffuse type, were grouped by microsatellite analysis into high-level MSI (MSI-H, n = 2), LOH (n = 5), and microsatellite stable, LOH not detected (MSS/LOH-N, n = 8) tumors. The DNA samples were subsequently analyzed by array comparative genomic hybridization with 16,000 cDNA clones. As expected, the LOH tumors showed more copy number changes; however, the frequency of small-size amplifications was similar across all tumor groups. In addition, the cDNA arrays detected two apparently single-gene amplicons, at 11q13 (CCND1) and 12p12.1 (K-RAS), the presence of which were confirmed using oligonucleotide arrays. A novel amplicon at 5q13.2 was found only in diffuse-type tumors, which were otherwise genetically stable. The results suggest that DNA copy number changes may also occur in gastric cancers that show genomic stability in microsatellite analysis.
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- 2006
15. DNA copy number aberrations in intestinal-type gastric cancer revealed by array-based comparative genomic hybridization
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Hanna Vauhkonen, Antti Sajantila, Sakari Knuutila, Pentti Sipponen, and Matti Vauhkonen
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Male ,Genome instability ,Cancer Research ,Gene Dosage ,Copy number analysis ,Loss of Heterozygosity ,Aneuploidy ,Biology ,Loss of heterozygosity ,03 medical and health sciences ,0302 clinical medicine ,Stomach Neoplasms ,Chromosomal Instability ,Chromosome instability ,Genetics ,medicine ,Humans ,neoplasms ,Molecular Biology ,Aged ,Oligonucleotide Array Sequence Analysis ,030304 developmental biology ,Aged, 80 and over ,0303 health sciences ,Nucleic Acid Hybridization ,Microsatellite instability ,DNA, Neoplasm ,Sequence Analysis, DNA ,Middle Aged ,medicine.disease ,Molecular biology ,digestive system diseases ,030220 oncology & carcinogenesis ,Female ,DNA mismatch repair ,Microsatellite Repeats ,Comparative genomic hybridization - Abstract
Genomic instability can be divided into 2 categories: chromosomal instability (CIN) and microsatellite instability (MSI). CIN has been linked to aneuploidy and chromosomal aberrations, and high-level loss of heterozygosity (LOH-H) has been suggested to be an indicator of CIN. High-level MSI (MSI-H), which results from nonfunctional mismatch repair, has previously been suggested to be mutually exclusive with CIN. Four MSI-H and three LOH-H primary gastric tumors of intestinal histology were used for copy number analysis by array-based comparative genomic hybridization (aCGH) with 13,000 cDNA targets. The MSI-H group showed fewer gains (0-12, average 4.5) and losses (0-10, average 2.5) per tumor as compared to the LOH-H group (9-15 gains, average 11.6 and 1-6 losses, average 4). Two MSI-H tumors did not show any copy number changes and one showed only gains of whole chromosomes. The most common alterations were gains of 20q (5/7 samples), 1q, 8, and 10p (3/7 samples) and losses of 1p and 5p (3/7 samples). The minimal amplified regions in 1q and 20q were localized to 1q21.1 approximately q21.2, 1q21.3, 20q11.2, 20q13.12, and 20q13.3 approximately qter. No copy number change was found to be specific for MSI-H or LOH-H. The results suggest that the LOH-H phenotype revealed by microsatellite analysis predicts reliably copy number abnormalities on aCGH and that a subset of MSI-H and all LOH-H tumors share the CIN phenotype.
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- 2006
16. Pathology and molecular biology of gastric cancer
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Pentti Sipponen, Hanna Vauhkonen, and Matti Vauhkonen
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Pathology ,medicine.medical_specialty ,Atrophic gastritis ,Molecular pathology ,Gastroenterology ,Cancer ,Intestinal metaplasia ,Microsatellite instability ,DNA, Neoplasm ,Gene mutation ,Biology ,medicine.disease ,Gene Expression Regulation, Neoplastic ,Loss of heterozygosity ,Stomach Neoplasms ,Dysplasia ,Mutation ,Biomarkers, Tumor ,Disease Progression ,medicine ,Humans ,Neoplasm Staging - Abstract
Several attempts to classify gastric cancer (GCA) have been made over the past decades. Most successful, and widely used, is the classification by Lauren, which distinguishes, by microscopical morphology alone, two main cancer pathogeneses, diffuse (DGCA) and intestinal (IGCA) subtypes, which appear clearly as dissimilar clinical and epidemiological entities. Here we review the main differences in epidemiology, histopathology, and molecular pathology of the two main subtypes of gastric carcinomas based on Lauren classification. In clinical practice, however, clinical staging, particularly in predicting the survival, still remains superior to all classifications of gastric cancer independent of cancer type. The existence of local precursor lesions or conditions of IGCA tumours, i.e. Helicobacter pylori gastritis, atrophic gastritis (AG), intestinal metaplasia (IM), adenoma, dysplasia, and intramucosal neoplasia, is firmly established. The links of DGCA with intestinal-type epithelium, AG or IM are poor, or do not exist. So far, H. pylori gastritis is the only universal precursor condition for DGCA. It implies that AG and achlorhydria are of minor significance and infrequent in the development of DGCA but are important steps in that of IGCA. Despite an increasing body of data, the overall view on molecular pathology of GCA remains fragmentary. No consistent differences in the molecular pathology of GCA subtypes to meet the Lauren classification have been established. With the exception of TP53 , no gene mutation occurring regularly in both histological types of GCA has been reported. Chromosomal aberrations and loss of heterozygosity seem to be non-specific and do not follow any consistent route in the progression of GCA. Microsatellite instability is more commonly found in IGCA than in DGCA. The present epigenetic data suggest that most of the decrease (or loss) of gene expression may be explained by promoter hypermethylation which is more often found in IGCA. In DGCA specific genes such as CDH1 are more often hypermethylated. Compared with GCA, in premalignant condition lesions gene mutations and chromosomal aberrations are infrequent. Epigenetic dysregulation might also represent a major mechanism for altered gene expression in premalignant stages in gastric carcinogenesis.
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- 2006
17. Gene copy number changes in dermatofibrosarcoma protuberans – a fine-resolution study using array comparative genomic hybridization
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Hanna Vauhkonen, Fredrik Mertens, Nils Mandahl, Tom Böhling, Sakari Knuutila, and Sippy Kaur
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Adult ,Male ,medicine.medical_specialty ,Skin Neoplasms ,Gene Dosage ,Chromosomal translocation ,Biology ,Chromosomes ,Collagen Type I ,Translocation, Genetic ,Neoplasms ,Genetics ,Dermatofibrosarcoma protuberans ,medicine ,Humans ,Supernumerary ,Copy-number variation ,Molecular Biology ,Gene ,Genetics (clinical) ,PDGFB ,Dermatofibrosarcoma ,Computational Biology ,Nucleic Acid Hybridization ,Middle Aged ,medicine.disease ,Molecular biology ,Collagen Type I, alpha 1 Chain ,Cytogenetic Analysis ,Medical genetics ,Female ,Comparative genomic hybridization - Abstract
Dermatofibrosarcoma protuberans (DFSP) is a rare, slow-growing, low-grade dermal tumor. Cytogenetic and FISH studies have revealed that the chromosomal rearrangements characteristic of DFSP tumors involve both translocations and the formation of a supernumerary ring derived from chromosomes 17 and 22. The t(17;22) (q22;q13.1) translocation generates a gene fusion between COL1A1 and PDGFB, which serves as a diagnostic marker of DFSP. In the present study we performed array-CGH (aCGH) analysis on ten DFSP tumors. The COL1A1 region at 17q was gained in 71% (5/7) of the samples and the PDGFB region at 22q was gained in 43% (3/7) of the individual samples. In addition to the 17q and 22q gains, altogether 17 minimal common regions of gain and one region of loss were detected.
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- 2006
18. Intrinsic structural variation of the complex microsatellite marker MYCL1 in Finnish and Somali populations and its relevance to gastrointestinal tumors
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Antti Sajantila and Hanna Vauhkonen
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Gastrointestinal tumors ,lcsh:QH426-470 ,gastrointestinal tumors ,Population ,Biology ,Somali ,Structural variation ,03 medical and health sciences ,0302 clinical medicine ,Genetics ,MYCL1 ,medicine ,Allele ,education ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,education.field_of_study ,Finnish and Somali populations ,Microsatellite instability ,medicine.disease ,language.human_language ,complex microsatellite ,lcsh:Genetics ,030220 oncology & carcinogenesis ,language ,Microsatellite ,microsatellite instability ,colorectal cancers - Abstract
The structurally complex MYCL1 microsatellite marker is often used to determine microsatellite instability in colorectal cancers but the allelic variation of this marker has remained largely uncharacterized in both populations and in cancers. Our study describes the allelic distributions of MYCL1 in Finnish (n = 117) and Somali population samples (n = 61) of non-related individuals and compares this distribution with the instability pattern obtained from 61 gastrointestinal tumors.
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- 2006
19. Differences in genomic instability between intestinal- and diffuse-type gastric cancer
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Antti Sajantila, Hanna Vauhkonen, Matti Vauhkonen, and Pentti Sipponen
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Male ,Genome instability ,Cancer Research ,Pathology ,medicine.medical_specialty ,Chromosomes, Human, Pair 21 ,Intestinal Neoplasm ,Loss of Heterozygosity ,Genome ,Genomic Instability ,Loss of heterozygosity ,Stomach Neoplasms ,Surgical oncology ,Intestinal Neoplasms ,medicine ,Humans ,Stomach cancer ,neoplasms ,Aged ,Neoplasm Staging ,Chromosome Aberrations ,business.industry ,Gastroenterology ,Microsatellite instability ,Cancer ,DNA, Neoplasm ,General Medicine ,Prognosis ,medicine.disease ,digestive system diseases ,stomatognathic diseases ,Oncology ,Chromosomes, Human, Pair 5 ,Female ,Chromosomes, Human, Pair 18 ,business ,Microsatellite Repeats - Abstract
Microsatellite instability (MSI) and loss of heterozygosity (LOH) are lesions in the genome found with different frequencies in gastric carcinomas (GCAs). Despite a great body of studies, no systematic approach to the detailed classification of MSI and LOH in the two major types of GCA has been published.Thirty-seven advanced GCAs, 25 intestinal-type (IGCAs) and 12 diffuse-type (DGCAs), were assayed with 15 autosomal tetranucleotide markers on 14 chromosomal arms. The observed frequencies and types of microsatellite alterations allowed stratification into subgroups, i.e., high- and low-grade MSI (MSI-H, MSI-L) or microsatellite-stable (MSS), and high- or low-grade, or non-detectable LOH (LOH-H, LOH-L, LOH-N).Collectively, the markers detected MSI-H tumors with sensitivity equal to that of BAT-26 (a single marker highly specific for MSI-H). Likewise, the markers detected LOH at chromosomal arms 5q, 18q, and 21q with a sensitivity equal to markers used previously. Seven (19%) MSI-H and six (16%) LOH-H tumors were found, with a significant association (P = 0.027) with IGCA: 92% of MSI-H and LOH-H occurred in IGCA patients only. Conversely, in DGCA, a significantly higher prevalence of a stable (LOH-N/MSS) phenotype was found as compared with IGCA (75.1% vs 28.0%; P = 0.035). The MSI-L phenotype was found in 57.9% of non-MSI-H IGCA tumors and was associated significantly (P = 0.015) with LOH-H.A clear difference in genomic instability between IGCA and DGCA was found. In IGCA, the MSI and LOH pathways were more commonly involved, whereas in DGCA, a stable phenotype was predominant. As a novel finding, MSI-L as a true phenomenon and its association with LOH was observed in IGCA.
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- 2005
20. Genome-wide differences between microsatellite stable and unstable colorectal tumors
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Hanna Vauhkonen, Josep Egozcue, Jordi Camps, Sakari Knuutila, Esther Prat, Juan José Lozano, Gemma Armengol, Javier del Rey, Rosa Miró, and Lauro Sumoy
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Male ,Cancer Research ,Gene Dosage ,Biology ,medicine.disease_cause ,Genome ,Genomic Instability ,medicine ,Humans ,neoplasms ,Gene ,Metaphase ,Aged ,Genetics ,Gene Expression Profiling ,Cancer ,Microsatellite instability ,General Medicine ,Middle Aged ,medicine.disease ,Molecular biology ,digestive system diseases ,Phenotype ,Microsatellite ,Female ,Colorectal Neoplasms ,Carcinogenesis ,Microsatellite Repeats ,Comparative genomic hybridization - Abstract
Genomic copy number changes are frequently found in cancers and they have been demonstrated to contribute to carcinogenesis; and it is widely accepted that tumors with microsatellite instability (MSI) are genetically stable and mostly diploid. In the present study we compared the copy number alterations and the gene-expression profiles of microsatellite stable (MSS) and MSI colorectal tumors. A total number of 31 fresh-frozen primary tumors (16 MSS and 15 MSI) were used. Twenty-eight samples (15 MSS and 13 MSI) were analyzed with metaphase comparative genomic hybridization (CGH), nine of which plus one additional sample (4 MSS and 6 MSI) were further analyzed by cDNA-based array-CGH. Gene expression analysis was performed with six samples [3 MSS and 3 MSI, four of these used in metaphase CGH (mCGH) analysis] to identify differentially expressed genes possibly located in the lost or amplified regions found by CGH, stressing the biological significance of copy number changes. Metaphase and array-CGH analysis of two colon cancer cell lines (HTC116 and SW480, reported as MSI and MSS archetypes) gave comparable results. Alterations found by mCGH in MSS tumors were +20, +8q, -8p and -18q. Interestingly, 1p22, 4q26 and 15q21 were found deleted preferentially in MSS tumors, while 22q13 was found gained in MSI tumors. The regions of alterations identified by array-CGH were gains at 8q24, 16q24.3 and 20q13, and the loss of 5q21, appearing in the both types of tumors. Gene expression analysis revealed genes with specific associations with the copy number changes of the corresponding genomic regions. As a conclusion, colorectal cancer is a heterogeneous disease, demonstrated by the genomic profiles of individual samples. However, our data shows that copy number changes do not occur exclusively in the MSS phenotypes.
- Published
- 2005
21. Correlation Between the Allelic Distribution of STRs in a Finnish Population and Phenotypically Different Gastrointestinal Tumours: A Study Using Four X-Chromosomal Markers (DXS7423, DXS8377, ARA, DXS101)
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Matti Vauhkonen, Antti Sajantila, Hanna Vauhkonen, and Pentti Sipponen
- Subjects
Genetics ,0303 health sciences ,education.field_of_study ,Korean population ,Population ,Microsatellite instability ,Biology ,medicine.disease ,Molecular biology ,humanities ,Correlation ,03 medical and health sciences ,0302 clinical medicine ,Finnish population ,medicine ,Microsatellite ,030216 legal & forensic medicine ,Allele ,education ,Allele frequency ,Genetics (clinical) ,030304 developmental biology - Abstract
Summary Microsatellite instability in tumours has been suggested as a model to study the process of short tandem repeat (STR) mutations. In the present study we have determined the allelic variation of four X-STRs (DXS7423, DXS8377, DXS101 and ARA) in a Finnish population of 103 individuals, and assessed whether a comparable allelic distribution could be found in a series of gastrointestinal cancers differing by the level of microsatellite instability. Fifty-seven gastric and colorectal cancers were stratified by autosomal STRs, and the mononucleotide marker BAT-26 into stable, low-level unstable and high-level unstable microsatellite (MSI-H) cancers, of which the last produced the majority of X-STR alleles. For the four markers analysed, a significant correlation of allele distribution between our Finnish population sample and MSI-H tumours was noted. Together, the eight MSI-H tumours found represented 80%, 66–80% and 100% of the DXS101 alleles in the Finnish, and in previously described Caucasian and Korean population samples, respectively. Of the ARA, DXS7423 and DXS8377 alleles in the Finnish population, 42%, 75% and 79% were found in the MSI-H cancers, respectively. The results suggest that analysis of STR variation in a relatively small number of MSI-H cancers may aid in pre-evaluation of their allelic distribution in a population.
- Published
- 2004
22. Evaluation of gastrointestinal cancer tissues as a source of genetic information for forensic investigations by using STRs
- Author
-
Matti Vauhkonen, Hanna Vauhkonen, Antti Sajantila, Pentti Sipponen, Matti Kataja, and Minttu Hedman
- Subjects
Genetic Markers ,Male ,Sex Determination Analysis ,Pathology ,medicine.medical_specialty ,Loss of Heterozygosity ,Locus (genetics) ,Biology ,Pathology and Forensic Medicine ,law.invention ,Loss of heterozygosity ,03 medical and health sciences ,0302 clinical medicine ,Dental Enamel Proteins ,law ,medicine ,Humans ,030216 legal & forensic medicine ,Typing ,Gastrointestinal cancer ,neoplasms ,Polymerase chain reaction ,Aged ,Gastrointestinal Neoplasms ,Aged, 80 and over ,Genetics ,Amelogenin ,Genetic Variation ,Tooth Germ ,Microsatellite instability ,Middle Aged ,medicine.disease ,DNA Fingerprinting ,digestive system diseases ,3. Good health ,Phenotype ,DNA profiling ,Tandem Repeat Sequences ,030220 oncology & carcinogenesis ,Mutation ,Microsatellite ,Female ,Law - Abstract
Malignant tissue samples may sometimes be the only source of biological material for forensic investigations, including identification of individuals or paternity testing. However, in use of such samples, uncertainties due to microsatellite instability (MSI) and loss of heterozygosity (LOH) often associated with neoplasias may be encountered. In this study, we have analysed the applicability of autosomal tetranucleotide short tandem repeat (STR) markers, which are routinely used in forensic analysis, to gain genetic information. MSI and LOH were analysed in 41 surgically removed gastrointestinal cancer specimens and the adjascent non-cancerous tissue marginals. The cancer specimens showed great variability in their genetic phenotypes due to MSI or LOH, with only 32% being microsatellite-stable. Of the 15 autosomal STR loci analysed, only TH01 had no MSI-type alteration in these samples. The loci most frequently affected by MSI were D8S1179, D21S11, D18S51 and D19S433 (MSI in 15–17% of cases). LOH-type alterations were observed at all of the loci, including the amelogenin locus used for sex determination. The highest LOH frequency was found at locus D18S51 (27%). The genetic alterations at the marker loci may indicate false homozygosity or heterozygosity, and false gender may result from erroneous deduction of DNA profiles. Therefore, typing of autosomal STRs from malignant tissues in forensic settings warrants careful interpretation of MSI and LOH results together with microscopic analysis of a tissue specimen. Results by two commercially available and widely used forensic DNA profiling kits used here were comparable.
- Published
- 2004
23. Typing of XY (male) Genotype from Malignant Neoplastic Tissue by the Amelogenin-based Sex Test
- Author
-
Minttu Hedman, Antti Sajantila, Pentti Sipponen, Matti Vauhkonen, and Hanna Vauhkonen
- Subjects
Male ,Sex Determination Analysis ,Pathology ,medicine.medical_specialty ,Genotype ,Loss of Heterozygosity ,Locus (genetics) ,Biology ,Y chromosome ,Pathology and Forensic Medicine ,Loss of heterozygosity ,03 medical and health sciences ,0302 clinical medicine ,Dental Enamel Proteins ,stomatognathic system ,Genetics ,medicine ,Humans ,Typing ,Allele ,DNA Primers ,Gastrointestinal Neoplasms ,030304 developmental biology ,Chromosomes, Human, X ,0303 health sciences ,Chromosomes, Human, Y ,Amelogenin ,Tooth Germ ,Molecular biology ,Phenotype ,DNA profiling ,Tandem Repeat Sequences ,Case-Control Studies ,030220 oncology & carcinogenesis ,Forensic Anthropology ,Microsatellite - Abstract
DNA profiling of a cancer tissue can be problematic because of genomic instability. Here we have analyzed gastrointestinal cancer specimens from 46 males, of which seven (15%) showed aberrations in determination of gender by the widely used amelogenin test. The X-type amelogenin allele in all cases remained intact. All male tumor samples showing frequent autosomal loss of heterozygosity had a decreased signal of the Y allele from the amelogenin marker. When tested with an alternate set of primers for the amelogenin locus, the Y-type allele showed loss of heterozygosity in the same seven cases. However, when amplified with 15 Y-specific STR primers, all the cancerous tissue Y chromosomes seemed to be intact. These results indicate when malignant neoplastic tissue specimens are used, that amelogenin-based gender determination should be carefully interpreted.
- Published
- 2004
24. Correction: Copy Number Analysis of Complement C4A, C4B and C4A Silencing Mutation by Real-Time Quantitative Polymerase Chain Reaction
- Author
-
Hanna Vauhkonen, Asko Järvinen, Mikko Seppänen, Riitta Paakkanen, Marja-Liisa Lokki, and Katja T. Eronen
- Subjects
Multidisciplinary ,Actuarial science ,Competing interests ,Statement (logic) ,Science ,C4A ,Copy number analysis ,Correction ,Complement C4a ,Complement (complexity) ,Real-time polymerase chain reaction ,Mutation (genetic algorithm) ,Medicine ,Business - Abstract
There was an error in the Competing Interests statement. The correct Competing interests are: MLL is working as a consultant at a company owned by the University of Helsinki providing complement C4 analysis for diagnostic samples. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials. The other authors have no competing interests to declare.
- Published
- 2012
25. Copy number analysis of complement C4A, C4B and C4A silencing mutation by real-time quantitative polymerase chain reaction
- Author
-
Katja T. Eronen, Riitta Paakkanen, Hanna Vauhkonen, Marja-Liisa Lokki, Mikko Seppänen, Asko Järvinen, Haartman Institute (-2014), Transplantation Laboratory, Kardiologian yksikkö, Department of Medicine, Infektiosairauksien yksikkö, and Clinicum
- Subjects
Low protein ,Complement System ,Gene Dosage ,COMPONENTS C4A ,Polymerase Chain Reaction ,DISEASE ,0302 clinical medicine ,Gene Frequency ,Gene Duplication ,Genetics of the Immune System ,Copy-number variation ,SYSTEMIC-LUPUS-ERYTHEMATOSUS ,RCCX MODULES ,Genetics ,0303 health sciences ,Multidisciplinary ,Complement C4a ,Null allele ,Innate Immunity ,Clinical Laboratory Sciences ,3. Good health ,DEFICIENCY ,Real-time polymerase chain reaction ,Infectious Diseases ,Phenotype ,030220 oncology & carcinogenesis ,POPULATIONS ,Medicine ,Research Article ,DNA Copy Number Variations ,Science ,Immunology ,education ,Copy number analysis ,Biology ,Real-Time Polymerase Chain Reaction ,Gene dosage ,Sensitivity and Specificity ,Autoimmune Diseases ,Immunophenotyping ,Molecular Genetics ,03 medical and health sciences ,Immune Deficiency ,Genetic Mutation ,Diagnostic Medicine ,Complement C4b ,Humans ,Genetic Testing ,Gene Silencing ,Allele frequency ,NULL ALLELES ,Genetic Association Studies ,Alleles ,030304 developmental biology ,DNA Primers ,Clinical Genetics ,Models, Genetic ,C4A ,Personalized Medicine ,Immunity ,Reproducibility of Results ,Human Genetics ,Molecular biology ,GENE ,POLYMORPHISM ,Gene Expression Regulation ,Immune System ,3121 General medicine, internal medicine and other clinical medicine ,Genetics of Disease ,Mutation ,RISK-FACTORS ,Clinical Immunology ,3111 Biomedicine - Abstract
Low protein levels and copy number variation (CNV) of the fourth component of human complement (C4A and C4B) have been associated with various diseases. High-throughput methods for analysing C4 CNV are available, but they commonly do not detect the most common C4A mutation, a silencing CT insertion (CTins) leading to low protein levels. We developed a SYBR® Green labelled real-time quantitative polymerase chain reaction (qPCR) with a novel concentration range approach to address C4 CNV and deficiencies due to CTins. This method was validated in three sample sets and applied to over 1600 patient samples. CTins caused C4A deficiency in more than 70% (76/105) of the carriers. Twenty per cent (76/381) of patients with a C4A deficiency would have been erroneously recorded as having none, if the CTins had not been assessed. C4A deficiency was more common in patients than a healthy reference population, (OR = 1.60, 95%CI = 1.02–2.52, p = 0.039). The number of functional C4 genes can be straightforwardly analyzed by real-time qPCR, also with SYBR® Green labelling. Determination of CTins increases the frequency of C4A deficiency and thus helps to elucidate the genotypic versus phenotypic disease associations.
- Published
- 2012
26. HLA-DRB1 allele frequencies and C4 copy number variation in Finnish sarcoidosis patients and associations with disease prognosis
- Author
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Anil Palikhe, Marja-Liisa Lokki, Annika Wennerström, Laura Lahtela, Jouni Hedman, Essi Varkki, Hanna Vauhkonen, Anne Pietinalho, Olof Selroos, Mikko Seppänen, and Minna Purokivi
- Subjects
musculoskeletal diseases ,Adult ,Male ,DNA Copy Number Variations ,Genotype ,Sarcoidosis ,Immunology ,Disease ,Linkage Disequilibrium ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Gene Frequency ,medicine ,Complement C4b ,Immunology and Allergy ,Humans ,Genetic Predisposition to Disease ,Copy-number variation ,Allele ,skin and connective tissue diseases ,HLA-DRB1 ,Allele frequency ,Alleles ,Finland ,030304 developmental biology ,0303 health sciences ,business.industry ,Complement C4a ,General Medicine ,Odds ratio ,Middle Aged ,medicine.disease ,Prognosis ,3. Good health ,Logistic Models ,Haplotypes ,Etiology ,Female ,business ,030215 immunology ,HLA-DRB1 Chains - Abstract
Sarcoidosis is a multiorgan immune-mediated disease of unknown etiology with varying clinical pictures. We studied 3 genes in the major histocompatibility complex region (HLA-DRB1 and complement C4A and C4B) in patients with resolved disease after a 2-year follow-up (n = 90) and in patients whose disease was still active at that time point (n = 98) and compared them with controls (n = 150). Our primary aim was to detect genetic differences between the patient groups. We observed that the susceptibility allele for sarcoidosis was HLA-DRB1*15:01 (p = 0.011; odds ratio [OR] = 1.67) and the protective allele was HLA-DRB1*01:01 (p = 0.001; OR = 0.43). HLA-DRB1*03:01 was associated with resolving disease when compared with the persistent group (p = 0.011; OR = 2.22). The probability of having resolving disease was even greater if the patient had HLA-DRB1*03:01 and did not have extrapulmonary lesions (p = 0.001; OR = 3.39). By evaluating amino acid variants of the HLA-DRB1 gene, we determined that specific amino acids in pockets 4, 7, and 9 were associated with the prognosis of sarcoidosis. Our results support the importance of HLA-DRB1 as a predisposing gene for sarcoidosis. Particularly, HLA-DRB1*03:01 and polymorphisms of DRB1 pocket residues were associated with a favorable prognosis. Thus, accurate categorization of disease phenotype and HLA-DRB1 sequencing offer a basis for disease course estimation of sarcoidosis.
- Published
- 2011
27. Beneficial effect of clarithromycin in patients with acute coronary syndrome and complement C4 deficiencies
- Author
-
Hanna Vauhkonen, Marja-Liisa Lokki, Anil Palikhe, Juha Sinisalo, Pekka Saikku, Riitta Paakkanen, Mikko Seppänen, and Markku S. Nieminen
- Subjects
Male ,Acute coronary syndrome ,medicine.medical_specialty ,Heart disease ,medicine.drug_class ,Antibiotics ,030204 cardiovascular system & hematology ,Placebo ,Coronary artery disease ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Clarithromycin ,medicine ,Humans ,Myocardial infarction ,Acute Coronary Syndrome ,030304 developmental biology ,Aged ,0303 health sciences ,business.industry ,C4A ,Complement C4 ,Chlamydophila pneumoniae ,Middle Aged ,medicine.disease ,3. Good health ,Surgery ,Anti-Bacterial Agents ,Female ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug - Abstract
We sought to examine the role of complement component C4 deficiencies on the effect of antibiotic treatment in patients with acute coronary syndrome (ACS).Patients with ACS (n=144) were randomly divided to receive a three-month treatment of clarithromycin or placebo and followed for major adverse coronary and cerebrovascular events (MACCEs) for 404.5 median days (range 138-924 days). The primary results indicated that clarithromycin prevented recurrent cardiovascular attacks. For the present study we performed serum C4 allotyping of C4A and C4B. The clarithromycin response was reanalyzed taking into account the deficiencies in the C4 allotypes.The prevalence of C4A deficiency, C4B deficiency or these combined were 29.2% (42/144), 39.6% (57/144) and 66.0% (95/144), respectively. In patients with C4 deficiencies clarithromycin treatment resulted in a reduced number of MACCEs and the best cumulative survival as compared with the placebo group (MACCE 18.8% versus 39.1%, respectively; Log rank test, p=0.015).Only patients with ACS and C4 deficiencies seem to benefit from antibiotic treatment. This may explain the controversial results of secondary prevention trials of coronary artery disease and possibly serve as a pharmacogenomic marker for clarithromycin treatment.
- Published
- 2009
28. Helicobacter pylori infection induces a reversible expression of the CDX2 transcription factor protein in human gastric epithelium
- Author
-
Matti Vauhkonen, Hanna Vauhkonen, and Pentti Sipponen
- Subjects
Adult ,Male ,medicine.medical_specialty ,Pathology ,Time Factors ,Biopsy ,Gastroenterology ,Helicobacter Infections ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Gastric mucosa ,Humans ,CDX2 Transcription Factor ,CDX2 ,Antrum ,030304 developmental biology ,Aged ,Aged, 80 and over ,Homeodomain Proteins ,0303 health sciences ,biology ,Helicobacter pylori ,Stomach ,Intestinal metaplasia ,Epithelial Cells ,Middle Aged ,biology.organism_classification ,medicine.disease ,Antibodies, Bacterial ,Immunohistochemistry ,digestive system diseases ,3. Good health ,medicine.anatomical_structure ,Gastric Mucosa ,Gastritis ,embryonic structures ,030211 gastroenterology & hepatology ,Female ,medicine.symptom ,Immunostaining ,Biomarkers ,Follow-Up Studies - Abstract
The homeobox gene CDX2 is implicated in the appearance of intestinal metaplasia in Helicobacter pylori gastritis. The aim of this study was to investigate whether CDX2 expression in gastric mucosa occurs before the appearance of overt intestinal metaplasia in H. pylori gastritis, and whether or not this expression is reversible.CDX2 was studied by immunohistochemistry in a cohort of 38 patients with H. pylori gastritis before and after eradication (mean follow-up 6.3 years) of H. pylori. A cohort of 49 individuals with healthy stomachs was analysed as a control.In the control group no immunostaining of CDX2 in the epithelial cells of the gastric body was found, while in 57% of the cases a mild, aberrant nuclear immunostaining of CDX2 in the non-metaplastic epithelial cells in antrum, designated as "positive staining of single cells" (PSSC), was found. In H. pylori gastritis, the PSSC was seen in antrum and corpus in 100% and 26% of the cases, respectively. The prevalence of antral PSSC was significantly increased (on average by 4-fold) in H. pylori gastritis as compared with controls. After eradication of H. pylori, the prevalence of PSSC decreased significantly in antrum but not in corpus.Expression of CDX2 at low intensity is common in the epithelium of normal antrum, and this expression is enhanced in H. pylori gastritis. Expression of CDX2 is reversible at least in antrum after eradication of H. pylori infection.
- Published
- 2008
29. Can bladder adenocarcinomas be distinguished from schistosomiasis-associated bladder cancers by using array comparative genomic hybridization analysis?
- Author
-
Hanna Vauhkonen, Sakari Knuutila, Saad Eissa, Sohair Shoman, and Tom Böhling
- Subjects
Male ,Cancer Research ,Gene Dosage ,Schistosomiasis ,Biology ,Malignancy ,DNA Copy Number Changes ,Genetics ,medicine ,Chromosomes, Human ,Humans ,Lymphocytes ,Molecular Biology ,Aged ,Neoplasm Staging ,Oligonucleotide Array Sequence Analysis ,Carcinoma, Transitional Cell ,Squamous cell cancer ,Bladder cancer ,Gene Expression Profiling ,Nucleic Acid Hybridization ,DNA, Neoplasm ,Middle Aged ,medicine.disease ,Transitional cell carcinoma ,Urinary Bladder Neoplasms ,Case-Control Studies ,Karyotyping ,Cancer research ,Transitional Cell ,Carcinoma, Squamous Cell ,Female ,Comparative genomic hybridization - Abstract
Bladder cancer is the most common malignancy in many tropical and subtropical areas, correlating well with the endemicity of schistostomiasis. The majority of schistostomiasis-associated (SA) bladder cancers are squamous cell cancers, whereas the majority of non-SA cases in the Western world are transitional cell cancers, suggesting different carcinogenetic mechanisms. Approximately 6% of SA and 1% of non-SA cases are adenocarcinomas. To achieve fine-resolution information of DNA copy number changes in SA adenocarcinomas, 10 tumor samples were analyzed on an oligonucleotide-based CGH array. The frequency of aberrations ranged from 2 to 17, with an average of 10 alterations per sample. The most frequently gained regions were 20q and 8q (in 70 and 60% of the cases, respectively), whereas the most frequently lost regions were 5q and 8p (both in 40% of the cases). In addition, six regions of amplification were found in three samples, containing both well characterized and novel regions. Comparison of the DNA copy number profiles to previously reported profiles of SA transitional cell carcinoma and squamous cell carcinoma revealed similarities (e.g., gains at 5p and 8q), as well as differences (e.g., TCC- and SCC-associated losses at 18p and 20p, and adenocarcinoma-associated gains at 20q). The results suggest that although SA cancers share genetic features, there also exist histology-specific regions of gain and loss.
- Published
- 2007
30. Molecular karyotyping in sarcoma diagnostics and research
- Author
-
Hanna, Vauhkonen, Suvi, Savola, Sippy, Kaur, Marcelo L, Larramendy, and Sakari, Knuutila
- Subjects
Neoplasms, Connective Tissue ,Karyotyping ,Humans ,Sarcoma ,Genetic Testing - Abstract
Conventional cytogenetic and molecular genetic studies have both clinical and biological significance in sarcomas. However, the resolution of these methods does not always suffice to screening of novel, specific genetic changes, such as small deletions, amplifications, and fusion genes. Tumor-specific chromosomal translocations revealed by cytogenetic and molecular methods play a decisive role in the differential diagnosis of sarcomas. The novel molecular karyotyping techniques have proven to be powerful in the screening of clinically and biologically relevant molecular changes in human neoplasias. A variety of platforms for molecular karyotyping is available, e.g., arrayed cDNA clones or oligonucleotides that can be used in microarray-based comparative genomic hybridization (CGH) and gene expression analysis. We review here the clinically most relevant cytogenetic and molecular changes in sarcomas and describe latest microarray techniques for screening of clinically relevant gene copy number and expression changes.
- Published
- 2006
31. New Insights into the Cellular Pathways Affected in Primary Uterine Leiomyosarcoma
- Author
-
Sippy, Kaur, Marcelo L, Larramendy, Massimiliano, Gentile, Catarina, Svarvar, Riitta, Koivisto-Korander, Hanna, Vauhkonen, Ilari, Scheinin, Arto, Leminen, Ralf, Bützow, Tom, Böhling, and Sakari, Knuutila
- Abstract
Resistance to chemotherapeutic agents and radiotherapy has kept surgery the primary treatment of uterine leiomyosarcoma (ULMS). In search of leads for potential therapeutic targets, array CGH (aCGH) was used to obtain a genomewide pattern of ULMS-specific genetic imbalances and to define the affected biological processes. Fine-resolution genomewide aCGH analysis was performed using customised 16K cDNA microarrays on 18 primary ULMS cases. Furthermore, patterns of DNA copy number changes were assessed for associations with clinical parameters, i.e., tumour grade, tumour size and patient status at last follow-up. Our aCGH results demonstrated extensive DNA copy number changes in all chromosomes. Of the 10,590 gene loci included in the analysis, 4,387 were found to be affected by DNA copy number gains and 4,518 by DNA copy number losses in at least one case. Further analyses revealed that 231 of these were commonly gained, and 265 lost in at least 20% of the cases. The gains affected loci at 1p, 1q, 2p, 3p, 6p, 8q, 10q and 18q, whereas losses were observed at 2q, 4q, 6p, 6q, 7p, 7q, 13q, 14p, 16q, 19p, Xp and Xq. Enrichment analysis of biological processes revealed the gained genes to be involved in the G1/S transition of mitotic cell cycle, co-translational protein targeting to membrane, actin filament polymerisation and positive regulation of cytokine biosynthesis, whereas the genes affected by losses were associated with DNA replication, chromatin modification, telomere maintenance, meiosis, mitosis and angiogenesis. These biological processes featured prominently two well-established tumour suppressors (BRCA2, EREG) and one proto-oncogene (GFI1). No statistically significant associations were found between the aberration patterns and clinical variables. Analysis of gene pathways using aCGH uncovered the biological networks involved in malignant progression of ULMS.
- Published
- 2006
32. Molecular Karyotyping in Sarcoma Diagnostics and Research
- Author
-
Suvi Savola, Hanna Vauhkonen, Marcelo L. Larramendy, Sakari Knuutila, and Sippy Kaur
- Subjects
Genetics ,0303 health sciences ,Microarray ,Karyotype ,Biology ,medicine.disease ,Synovial sarcoma ,3. Good health ,Fusion gene ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,medicine ,Clear-cell sarcoma ,Sarcoma ,Copy-number variation ,030304 developmental biology ,Comparative genomic hybridization - Abstract
Conventional cytogenetic and molecular genetic studies have both clinical and biological significance in sarcomas. However, the resolution of these methods does not always suffice to screening of novel, specific genetic changes, such as small deletions, amplifications, and fusion genes. Tumor-specific chromosomal translocations revealed by cytogenetic and molecular methods play a decisive role in the differential diagnosis of sarcomas. The novel molecular karyotyping techniques have proven to be powerful in the screening of clinically and biologically relevant molecular changes in human neoplasias. A variety of platforms for molecular karyotyping is available, e.g., arrayed cDNA clones or oligonucleotides that can be used in microarray-based comparative genomic hybridization (CGH) and gene expression analysis. We review here the clinically most relevant cytogenetic and molecular changes in sarcomas and describe latest microarray techniques for screening of clinically relevant gene copy number and expression changes.
- Published
- 2006
33. 212-P Allele and haplotype polymorphism of HLA-A, B, DRB1 and C4A/C4B loci in Finnish population
- Author
-
Hanna Vauhkonen, Anil Palikhe, Marja-Liisa Lokki, Annika Wennerström, Katja T. Eronen, and Mikko Seppänen
- Subjects
Genetics ,Finnish population ,Polymorphism (computer science) ,Immunology ,Haplotype ,C4A ,Immunology and Allergy ,General Medicine ,Biology ,Allele ,HLA-A - Published
- 2011
34. MHC-related risk markers for coronary artery disease—Special emphasis on C4
- Author
-
Riitta Paakkanen, Pekka Saikku, Anil Palikhe, Mikko Seppänen, Hanna Vauhkonen, Marja-Liisa Lokki, Markku S. Nieminen, and Juha Sinisalo
- Subjects
medicine.medical_specialty ,Framingham Risk Score ,biology ,business.industry ,Immunology ,medicine.disease ,Major histocompatibility complex ,Coronary artery disease ,Internal medicine ,Cardiology ,medicine ,biology.protein ,business ,Molecular Biology - Published
- 2009
35. Genome-wide differences between microsatellite stable and unstable colorectal tumors.
- Author
-
Gemma Armengol, Juan José Lozano, Hanna Vauhkonen, Lauro Sumoy, and Sakari Knuutila
- Abstract
Genomic copy number changes are frequently found in cancers and they have been demonstrated to contribute to carcinogenesis; and it is widely accepted that tumors with microsatellite instability (MSI) are genetically stable and mostly diploid. In the present study we compared the copy number alterations and the gene-expression profiles of microsatellite stable (MSS) and MSI colorectal tumors. A total number of 31 fresh-frozen primary tumors (16 MSS and 15 MSI) were used. Twenty-eight samples (15 MSS and 13 MSI) were analyzed with metaphase comparative genomic hybridization (CGH), nine of which plus one additional sample (4 MSS and 6 MSI) were further analyzed by cDNA-based array-CGH. Gene expression analysis was performed with six samples [3 MSS and 3 MSI, four of these used in metaphase CGH (mCGH) analysis] to identify differentially expressed genes possibly located in the lost or amplified regions found by CGH, stressing the biological significance of copy number changes. Metaphase and array-CGH analysis of two colon cancer cell lines (HTC116 and SW480, reported as MSI and MSS archetypes) gave comparable results. Alterations found by mCGH in MSS tumors were +20, +8q, −8p and −18q. Interestingly, 1p22, 4q26 and 15q21 were found deleted preferentially in MSS tumors, while 22q13 was found gained in MSI tumors. The regions of alterations identified by array-CGH were gains at 8q24, 16q24.3 and 20q13, and the loss of 5q21, appearing in the both types of tumors. Gene expression analysis revealed genes with specific associations with the copy number changes of the corresponding genomic regions. As a conclusion, colorectal cancer is a heterogeneous disease, demonstrated by the genomic profiles of individual samples. However, our data shows that copy number changes do not occur exclusively in the MSS phenotypes. [ABSTRACT FROM AUTHOR]
- Published
- 2006
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