20 results on '"Luqman Sulaiman"'
Search Results
2. Development of an Autonomous Unmanned Aerial Vehicle for Rapid Aircraft Defect Detection
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Hossain, Mohammad Sayeed, Afzal, Aftab, AlDhafari, Luqman Sulaiman, AlManai, Ahmed, AlBahrani, Raid Ibrahim, Khan, Abid Ali, editor, Hossain, Mohammad Sayeed, editor, Fotouhi, Mohammad, editor, Steuwer, Axel, editor, Khan, Anwar, editor, and Kurtulus, Dilek Funda, editor
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- 2024
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3. Design and Analysis of a Small-Scale Solar Powered UAV
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Anılır, Berkan, Afzal, Aftab, Al Abri, Omar Khalifa Said, Al Dhafari, Luqman Sulaiman Khamis, Khan, Abid Ali, Kurtuluş, Dilek Funda, Khan, Abid Ali, editor, Hossain, Mohammad Sayeed, editor, Fotouhi, Mohammad, editor, Steuwer, Axel, editor, Khan, Anwar, editor, and Kurtulus, Dilek Funda, editor
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- 2024
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4. Design and Analysis of Long Endurance Solar Powered UAV
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Al Dhafari, Luqman Sulaiman Khamis, Khan, Abid Ali, Al-Mahrouqi, Majid Abdullah Suleiman, Al Alawi, Mohammed Said Khamis, Al Ajmi, Abdullah Abdulameer Obaid, Al Zadjali, Hamza Hashim, Khan, Abid Ali, editor, Hossain, Mohammad Sayeed, editor, Fotouhi, Mohammad, editor, Steuwer, Axel, editor, Khan, Anwar, editor, and Kurtulus, Dilek Funda, editor
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- 2024
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5. Design of a Solar System UAV
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Al Majarfi, Younis Nasser Hamed, primary, Al Dhafari, Luqman Sulaiman Khamis, additional, Al Saqri, Lukman Saud Abdullah, additional, Roshdi, Abdulsalam Salim Dhahi A. L., additional, Al Riyami, Idris Mohamed Masoud, additional, and Al Kalbani, Azzam Yousuf Salim, additional
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- 2023
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6. Development of an Autonomous Unmanned Aerial Vehicle for Rapid Aircraft Defect Detection
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Hossain, Mohammad Sayeed, primary, Afzal, Aftab, additional, AlDhafari, Luqman Sulaiman, additional, AlManai, Ahmed, additional, and AlBahrani, Raid Ibrahim, additional
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- 2023
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7. Design and Analysis of Long Endurance Solar Powered UAV
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Al Dhafari, Luqman Sulaiman Khamis, primary, Khan, Abid Ali, additional, Al-Mahrouqi, Majid Abdullah Suleiman, additional, Al Alawi, Mohammed Said Khamis, additional, Al Ajmi, Abdullah Abdulameer Obaid, additional, and Al Zadjali, Hamza Hashim, additional
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- 2023
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8. Design and Analysis of a Small-Scale Solar Powered UAV
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Anılır, Berkan, primary, Afzal, Aftab, additional, Al Abri, Omar Khalifa Said, additional, Al Dhafari, Luqman Sulaiman Khamis, additional, Khan, Abid Ali, additional, and Kurtuluş, Dilek Funda, additional
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- 2023
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9. Genome-wide and locus specific alterations in CDC73/HRPT2-mutated parathyroid tumors.
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Luqman Sulaiman, Felix Haglund, Jamileh Hashemi, Takao Obara, Jörgen Nordenström, Catharina Larsson, and C Christofer Juhlin
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Medicine ,Science - Abstract
Mutations in the hyperparathyroidism type 2 (HRPT2/CDC73) gene and alterations in the parafibromin protein have been established in the majority of parathyroid carcinomas and in subsets of parathyroid adenomas. While it is known that CDC73-mutated parathyroid tumors display specific gene expression changes compared to CDC73 wild-type cases, the molecular cytogenetic profile in CDC73-mutated cases compared to unselected adenomas (with an expected very low frequency of CDC73 mutations) remains unknown. For this purpose, nine parathyroid tumors with established CDC73 gene inactivating mutations (three carcinomas, one atypical adenoma and five adenomas) were analyzed for copy number alterations and loss of heterozygosity using array-comparative genomic hybridization (a-CGH) and single nucleotide polymorphism (SNP) microarrays, respectively. Furthermore, CDC73 gene promoter methylation levels were assessed using bisulfite Pyrosequencing. The panel included seven tumors with single mutation and three with double mutations of the CDC73 gene. The carcinomas displayed copy number alterations in agreement with previous studies, whereas the CDC73-mutated adenomas did not display the same pattern of alterations at loci frequently deleted in unselected parathyroid tumors. Furthermore, gross losses of chromosomal material at 1p and 13 were significantly (p = 0.012) associated with parathyroid carcinomas as opposed to adenomas. Quantitative PCR-based copy number loss regarding CDC73 was observed in three adenomas, while all the carcinomas were diploid or showed copy number gain for CDC73 gene. Hypermethylation of the CDC73 gene promoter was not observed. Our data could suggest that CDC73-mutated parathyroid adenomas exhibit a partly unique cytogenetic profile in addition to that of carcinomas and unselected adenomas. Furthermore, CDC73-mutated carcinomas displayed losses at 1p and 13 which are not seen in CDC73-mutated adenomas, making these regions of interest for further studies regarding malignant properties in tumors from CDC73-mutated cases. However, due to the small sample size, validation of the results in a larger cohort is warranted.
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- 2012
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10. Molecular characterization of acquired tolerance of tumor cells to picropodophyllin (PPP).
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Jamileh Hashemi, Claire Worrall, Daiana Vasilcanu, Mårten Fryknäs, Luqman Sulaiman, Mohsen Karimi, Wen-Hui Weng, Weng-Onn Lui, Christina Rudduck, Magnus Axelson, Helena Jernberg-Wiklund, Leonard Girnita, Olle Larsson, and Catharina Larsson
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Medicine ,Science - Abstract
BACKGROUND: Picropodophyllin (PPP) is a promising novel anti-neoplastic agent that efficiently kills tumor cells in vitro and causes tumor regression and increased survival in vivo. We have previously reported that PPP treatment induced moderate tolerance in two out of 10 cell lines only, and here report the acquired genomic and expression alterations associated with PPP selection over 1.5 years of treatment. METHODOLOGY/PRINCIPAL FINDINGS: Copy number alterations monitored using metaphase and array-based comparative genomic hybridization analyses revealed largely overlapping alterations in parental and maximally tolerant cells. Gain/amplification of the MYC and PVT1 loci in 8q24.21 were verified on the chromosome level. Abnormalities observed in connection to PPP treatment included regular gains and losses, as well as homozygous losses in 10q24.1-q24.2 and 12p12.3-p13.2 in one of the lines and amplification at 5q11.2 in the other. Abnormalities observed in both tolerant derivatives include amplification/gain of 5q11.2, gain of 11q12.1-q14.3 and gain of 13q33.3-qter. Using Nexus software analysis we combined the array-CGH data with data from gene expression profilings and identified genes that were altered in both inputs. A subset of genes identified as downregulated (ALDH1A3, ANXA1, TLR4 and RAB5A) or upregulated (COX6A1, NFIX, ME1, MAPK and TAP2) were validated by siRNA in the tolerant or parental cells to alter sensitivity to PPP and confirmed to alter sensitivity to PPP in further cell lines. CONCLUSIONS: Long-term PPP selection lead to altered gene expression in PPP tolerant cells with increase as well as decrease of genes involved in cell death such as PTEN and BCL2. In addition, acquired genomic copy number alterations were observed that were often reflected by altered mRNA expression levels for genes in the same regions.
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- 2011
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11. Cancer Incidence in the Kurdistan Region of Iraq: Results of a Seven-Year Cancer Registration in Erbil and Duhok Governorates
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Karwan M-Amen, Omiad Abdullah, Ahmed Amin, Zeki Mohamed, Bestoon Hasan, Mudhir Shekha, Hastyar Najmuldeen, Fryad Rahman, Zjwan Housein, Ahmed Salih, Amin Mohammed, Luqman Sulaiman, Basak Barzingi, Dler Mahmood, Hemin Othman, Dara Mohammad, Fahmi Salih, Suad Ali, Trefa Mohamad, Kazhan Mahmood, Galawezh Othman, Mukhlis Aali, Govand Qader, Bashdar Hussen, Farhang Awla, Shahab Kareem, Fikry Qadir, Dilan Taher, and Abbas Salihi
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Adult ,Male ,Adolescent ,Incidence ,Infant, Newborn ,Infant ,General Medicine ,Middle Aged ,Young Adult ,Age Distribution ,Child, Preschool ,Neoplasms ,Iraq ,Humans ,Female ,Registries ,Sex Distribution ,Child ,Aged ,Retrospective Studies - Abstract
There are limited published data regarding the recent incidence trends of cancer in Iraqi Kurdistan.The present study assessed the epidemiological estimates of cancer incidence, as well providing a projection of future cancer trends in the upcoming decade by analysing the population-based cancer registry between 2013 and 2019, in both the Erbil and Duhok governorates. A retrospective analysis was performed on data retrieved from the Medical Statistics Department at the Ministry of Health, Kurdistan Regional Government (KRG).The total number of female cancer patients was higher in both governorates, and the total incidence of patients with cancer increased by over 2x between 2013 and 2019 in Erbil and Duhok, from 73 to 174 patients/100,000 individuals for women, and 36 to 85 patients/100,000 individuals for men. Analysis indicated that the percentage of patients with cancer is projected to increase by2x in the current decade, from 3,457 cases to 4,547 and 4,449 cases in the Erbil governorate; and from 1,365 to 2,633 and 2,737 cases in 2028 based on LSTM and bi-LTSM analysis in the Duhok governorate. Lung cancer (LC) and female breast cancer (BC) were the most prominent types of cancers diagnosed since 2013 in both the Erbil and Duhok governorates.The striking pattern of trends for both present and future cancer incidence rates require urgent solutions and comprehensive efforts to control risk factors that promote the increasing incidence of cancer in these two KRG governorates.br /.
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- 2022
12. Cancer Statistics in Kurdistan Region of Iraq: A Tale of Two Cities
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Dara K. Mohammad, Omiad Abdullah, Kazhan Mahmood, Hemin E. Othman, Dler Faieeq Darweesh Mahmood, Fahmi Salih, Farhang Ali Awla, Ahmed Salih, Fryad Rahman, Dilan Taher, Bashdar Mahmud Hussen, Hastyar Najmuldeen, Luqman Sulaiman, Abbas Salihi, Ahmed Amin, Mukhlis Aali, Mudhir Sabir Shekha, Galawezh Othman, Basak Barzingi, Bestoon Hasan, Zeki Mohamed, Fikry Ali Qadir, Karwan M-Amen, Zjwan Housein, Govand Qader, Trefa Mohamad, and Suad Khudhur Ali
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Geography ,Socioeconomics ,Cancer death - Abstract
There is limited published data on recent cancer incidence trends in Iraqi Kurdistan. Therefore, this study assesses epidemiological estimates of cancer incidence as well as the projection of future cancer trends in the upcoming decade by analysing the population-based cancer registry from 2013 to 2019 in both Erbil and Duhok governorates. A retrospective study was conducted on data retrieved from the Medical Statistics Department at the Ministry of Health, KRG. The total number of female cancer patients was higher in both governorates, and the total number of patients more than doubled from 2013 to 2019 in Erbil and Duhok, from 73 to 174 patients/100,000 population for women, and 36 to 85 patients/100,000 population for men. Data analysis indicates that the percentage of cancer patients is projected to increase in the decade from 2020-2030 from 107.4% to 234.3% in 2030 in Erbil governorate; and from 106% to 163% in Duhok governorate. Female breast cancer and lung cancer are the most prominent types of cancers since 2013 in Erbil and Duhok governorates. The striking pattern of trends for both present and future cancer incidence rates require the urgent solutions and comprehensive efforts to control risk factors that promote the continuity of cancer diseases in these two KRG governorates.
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- 2021
13. Amplification of 2p as a genomic marker for transformation in lymphoma
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Koichi Ichimura, Anna Kwiecinska, Luqman Sulaiman, Andrii Dinets, Svetlana Lagercrantz, Mattias Berglund, Anna Porwit, V. Peter Collins, and Catharina Larsson
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Adult ,Genetic Markers ,Male ,Cancer Research ,Adolescent ,Follicular lymphoma ,Biology ,Genome ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,CDKN2A ,Genetics ,medicine ,Humans ,Lymphoma, Follicular ,Gene ,Research Articles ,Aged ,Medicinsk genetik ,030304 developmental biology ,Aged, 80 and over ,Chromosome Aberrations ,Cancer och onkologi ,0303 health sciences ,NF-kappa B ,Middle Aged ,medicine.disease ,Lymphoma ,Transformation (genetics) ,Genetic marker ,Child, Preschool ,Chromosomes, Human, Pair 2 ,Cancer and Oncology ,030220 oncology & carcinogenesis ,Disease Progression ,Cancer research ,Female ,Lymphoma, Large B-Cell, Diffuse ,Medical Genetics ,Chromosomes, Human, Pair 17 ,Signal Transduction - Abstract
To outline further genetic mechanisms of transformation from follicular lymphoma (FL) to diffuse large B-cell lymphoma (DLBCL), we have performed whole genome array-CGH in 81 tumors from 60 patients [29 de novo DLBCL (dnDLBCL), 31 transformed DLBCL (tDLBCL), and 21 antecedent FL]. In 15 patients, paired tumor samples (primary FL and a subsequent tDLBCL) were available, among which three possessed more than two subsequent tumors, allowing us to follow specific genetic alterations acquired before, during, and after the transformation. Gain of 2p15–16.1 encompassing, among others, the REL, BCL11A, USP34, COMMD1, and OTX1 genes was found to be more common in the tDLBCL compared with dnDLBCL (P
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- 2014
14. Global hypomethylation and promoter methylation in small intestinal neuroendocrine tumors
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Catharina Larsson, Anders Höög, Luqman Sulaiman, Omid Fotouhi, Magnus Kjellman, Jan Zedenius, Jamileh Hashemi, and Maral Adel Fahmideh
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Cancer Research ,Candidate gene ,biology ,Methylation ,Molecular biology ,CDH1 ,Demethylating agent ,chemistry.chemical_compound ,chemistry ,DNA methylation ,Gene expression ,Cancer research ,biology.protein ,Molecular Biology ,Gene ,DNA - Abstract
Aberrant DNA methylation is a feature of human cancer affecting gene expression and tumor phenotype. Here, we quantified promoter methylation of candidate genes and global methylation in 44 small intestinal-neuroendocrine tumors (SI-NETs) from 33 patients by pyrosequencing. Findings were compared with gene expression, patient outcome and known tumor copy number alterations. Promoter methylation was observed for WIF1, RASSF1A, CTNNB1, CXCL14, NKX2–3, P16, LAMA1, and CDH1. By contrast APC, CDH3, HIC1, P14, SMAD2, and SMAD4 only had low levels of methylation. WIF1 methylation was significantly increased (P = 0.001) and WIF1 expression was reduced in SI-NETs vs. normal references (P = 0.003). WIF1, NKX2–3, and CXCL14 expression was reduced in metastases vs. primary tumors (P < 0.02). Low expression of RASSF1A and P16 were associated with poor overall survival (P = 0.045 and P = 0.011, respectively). Global methylation determined by pyrosequencing of LINE1 repeats was reduced in tumors vs. normal references, and was associated with loss in chromosome 18. The tumors fell into three clusters with enrichment of WIF1 methylation and LINE1 hypomethylation in Cluster I and RASSF1A and CTNNB1 methylation and loss in 16q in Cluster II. In Cluster III, these alterations were low-abundant and NKX2-3 methylation was low. Similar analyses in the SI-NET cell lines HC45 and CNDT2 showed methylation for CDH1 and WIF1 and/or P16, CXCL14, NKX2-3, LAMA1, and CTNNB1. Treatment with the demethylating agent 5-azacytidine reduced DNA methylation and increased expression of these genes in vitro. In conclusion, promoter methylation of tumor suppressor genes is associated with suppressed gene expression and DNA copy number alterations in SI-NETs, and may be restored in vitro.
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- 2014
15. TheVHL gene is epigenetically inactivated in pheochromocytomas and abdominal paragangliomas
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Fredrika Svahn, Martin Bäckdahl, Nimrod B Kiss, Luqman Sulaiman, C. Christofer Juhlin, Stefano Caramuta, Anders Höög, Adam Andreasson, and Catharina Larsson
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DNA promoter methylation ,Cancer Research ,SDHB ,Molecular Sequence Data ,Adrenal Gland Neoplasms ,Down-Regulation ,Pheochromocytoma ,Biology ,Epigenesis, Genetic ,Paraganglioma ,VHL ,medicine ,Humans ,MEN1 ,RNA, Messenger ,Epigenetics ,Promoter Regions, Genetic ,Molecular Biology ,Base Sequence ,qRT-PCR ,Methylation ,DNA Methylation ,medicine.disease ,Gene Expression Regulation, Neoplastic ,pyrosequencing ,Von Hippel-Lindau Tumor Suppressor Protein ,Abdominal Neoplasms ,Case-Control Studies ,DNA methylation ,gene expression ,Cancer research ,SDHD ,Research Paper - Abstract
Pheochromocytoma (PCC) and abdominal paraganglioma (PGL) are neuroendocrine tumors that present with clinical symptoms related to increased catecholamine levels. About a third of the cases are associated with constitutional mutations in pre-disposing genes, of which some may also be somatically mutated in sporadic cases. However, little is known about inactivating epigenetic events through promoter methylation in these very genes. Using bisulphite pyrosequencing we assessed the methylation density of 11 PCC/PGL disease genes in 96 tumors (83 PCCs and 13 PGLs) and 34 normal adrenal references. Gene expression levels were determined by quantitative RT-PCR. Both tumors and normal adrenal samples exhibited low methylation index (MetI) in the EGLN1 (PDH2), MAX, MEN1, NF1, SDHB, SDHC, SDHD, SDHAF2 (SDH5), and TMEM127 promoters, not exceeding 10% in any of the samples investigated. Aberrant RET promoter methylation was observed in two cases only. For the VHL gene we found increased MetI in tumors as compared with normal adrenals (57% vs. 27%; P < 0.001), in malignant vs. benign tumors (63% vs. 55%; P < 0.05), and in PGL vs. PCC (66% vs. 55%; P < 0.0005). Decreased expression of the VHL gene was observed in all tumors compared with normal adrenals (P < 0.001). VHL MetI and gene expressions were inversely correlated (R = −0.359, P < 0.0001). Our results show that the VHL gene promoter has increased methylation compared with normal adrenals (MetI > 50%) in approximately 75% of PCCs and PGLs investigated, highlighting the role of VHL in the development of these tumors.
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- 2013
16. Global and gene-specific promoter methylation analysis in primary hyperparathyroidism
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Omid Fotouhi, Catharina Larsson, Jamileh Hashemi, Inga-Lena Nilsson, Luqman Sulaiman, and C. Christofer Juhlin
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Adenoma ,Adult ,Male ,Cancer Research ,Candidate gene ,Biology ,Calcitriol receptor ,Epigenesis, Genetic ,Parathyroid Glands ,CDKN2A ,medicine ,Humans ,Epigenetics ,Promoter Regions, Genetic ,Molecular Biology ,Methylation ,DNA Methylation ,Hyperparathyroidism, Primary ,medicine.disease ,Molecular biology ,Gene Expression Regulation, Neoplastic ,Parathyroid Neoplasms ,CpG site ,DNA methylation ,Cancer research ,Female ,Primary hyperparathyroidism ,Research Paper - Abstract
Epigenetic mechanisms involved in primary hyperparathyroidism are poorly understood as studies are limited. In order to understand the role of aberrant DNA promoter methylation in the pathogenesis of parathyroid tumors, we have quantified the CpG island promoter methylation density of several candidate genes including APC (promoter 1A and 1B), ?-catenin (CTNNB1), CASR, CDC73/HRPT2, MEN1, P16 (CDKN2A), PAX1, RASSF1A, SFRP1 and VDR in 72 parathyroid tumors and 3 normal parathyroid references using bisulfite pyrosequencing. Global methylation levels were assessed for LINE-1. We also compared methylation levels with gene expression levels measured by qRT-PCR for genes showing frequent hypermethylation. The adenomas displayed frequent hypermethylation of APC 1A (37/66; 56%), RASSF1A (34/66; 52%) and ?-catenin (19/66; 29%). One of the three atypical adenomas was hypermethylated for APC 1A. The three carcinomas were hypermethylated for RASSF1A and SFRP1, and the latter was only observed in this subtype. The global methylation density was similar in tumors (mean 70%) and parathyroid reference samples (mean 70%). In general, hypermethylated genes had reduced expression in the parathyroid adenomas using qRT-PCR. Among the adenomas, methylation of APC 1A correlated with adenoma weight (r = 0.306, p < 0.05). Furthermore, the methylation status of RASSF1A correlated with each of APC 1A (r = 0.289, p < 0.05) and ?-catenin (r = 0.315, p < 0.01). Our findings suggest a role for aberrant DNA promoter methylation of APC 1A, ?-catenin and RASSF1A in a subset of parathyroid tumors.
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- 2013
17. Genetic characterization of large parathyroid adenomas
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Luqman Sulaiman, Felix Haglund, Anders Höög, Inga-Lena Nilsson, Catharina Larsson, Christofer Carl Juhlin, and Jamileh Hashemi
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Adenoma ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Proliferation index ,Endocrinology, Diabetes and Metabolism ,Gene Dosage ,Parathyroid hormone ,Biology ,Endocrinology ,Proto-Oncogene Proteins ,Internal medicine ,medicine ,Humans ,MEN1 ,Aged ,Aged, 80 and over ,Comparative Genomic Hybridization ,Parathyroid neoplasm ,Tumor Suppressor Proteins ,Regular Papers ,Chromosome ,Cancer ,Middle Aged ,medicine.disease ,CARD Signaling Adaptor Proteins ,Parathyroid Neoplasms ,Oncology ,Parathyroid Hormone ,Mutation ,Calcium ,Female ,Comparative genomic hybridization - Abstract
In this study, we genetically characterized parathyroid adenomas with large glandular weights, for which independent observations suggest pronounced clinical manifestations. Large parathyroid adenomas (LPTAs) were defined as the 5% largest sporadic parathyroid adenomas identified among the 590 cases operated in our institution during 2005–2009. The LPTA group showed a higher relative number of male cases and significantly higher levels of total plasma and ionized serum calcium (PMEN1mutations in five cases, and oneHRPT2(CDC73) mutation. Total or partial loss of parafibromin expression was observed in ten tumors, two of which also showed loss of APC expression. Using array CGH, we demonstrated recurrent copy number alterations most frequently involving loss in 1p (29%), gain in 5 (38%), and loss in 11q (33%). Totally, 21 minimal overlapping regions were defined for losses in 1p, 7q, 9p, 11, and 15q and gains in 3q, 5, 7p, 8p, 16q, 17p, and 19q. In addition, 12 tumors showed gross alterations of entire or almost entire chromosomes most frequently gain of 5 and loss of chromosome 11. While gain of 5 was the most frequent alteration observed in LPTAs, it was only detected in a small proportion (4/58 cases, 7%) of parathyroid adenomas. A significant positive correlation was observed between parathyroid hormone level and total copy number gain (r=0.48,P=0.031). These results support that LPTAs represent a group of patients with pronounced parathyroid hyperfunction and associated with specific genomic features.
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- 2012
18. Molecular characterization of parathyroid tumors from two patients with hereditary colorectal cancer syndromes
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Erik Björck, Catharina Larsson, Lucas Batista, Luqman Sulaiman, Gabriel Miltenberger-Miltenyi, Sónia do Vale, Joao Martin Martins, Florbela Ferreira, Felix Haglund, Adam Andreasson, Inga-Lena Nilsson, Anders Höög, and C. Christofer Juhlin
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Adenoma ,Male ,Cancer Research ,Pathology ,medicine.medical_specialty ,Proliferation index ,Tumor suppressor gene ,Adenomatous polyposis coli ,Colorectal cancer ,Adenomatous Polyposis Coli Protein ,Parafibromin ,Gene Dosage ,Copy number analysis ,Gene dosage ,Familial adenomatous polyposis ,Genetics ,medicine ,Humans ,Promoter Regions, Genetic ,Genetics (clinical) ,Adaptor Proteins, Signal Transducing ,Aged ,Aged, 80 and over ,biology ,Tumor Suppressor Proteins ,Nuclear Proteins ,DNA Methylation ,medicine.disease ,Gene Expression Regulation, Neoplastic ,Parathyroid Neoplasms ,Oncology ,Mutation ,biology.protein ,Cancer research ,Female ,MutL Protein Homolog 1 - Abstract
The tumor suppressor adenomatous polyposis coli (APC) has recently been implicated in parathyroid development. We here report clinical, histopathological and molecular investigations in parathyroid tumors arising in two patients; one familial adenomatous polyposis (FAP) syndrome patient carrying a constitutional APC mutation, and one Lynch syndrome patient demonstrating a germline MLH1 mutation as well as a non-classified, missense alteration of the APC gene. We sequenced the entire APC gene in tumor and constitutional DNA from both cases, assessed the levels of APC promoter 1A and 1B methylation by bisulfite Pyrosequencing analysis and performed immunohistochemistry for APC and parafibromin. In addition, copy number analysis regarding the APC gene on chromosome 5q21-22 was performed using qRT-PCR. Histopathological workup confirmed both tumors as parathyroid adenomas without signs of malignancy or atypia. No somatic mutations or copy number changes for the APC gene were discovered in the tumors; however, in both cases, the APC promoter 1A was hypermethylated while the APC promoter 1B was unmethylated. APC promoter 1B-specific mRNA and total APC mRNA levels were higher than in normal parathyroid samples. Immunohistochemical analyses revealed strong APC protein immunoreactivity and positive parafibromin expression in both parathyroid tumors. Absence of additional somatic APC mutations and copy number changes in addition to the positive APC immunoreactivity obtained suggest that the tumors arose without biallelic inactivation of the APC tumor suppressor gene. The finding of an unmethylated APC promoter 1B and high APC 1B mRNA levels could explain the maintained APC protein expression. Moreover, the findings of positive parafibromin and APC immunoreactivity as well as a low MIB-1 proliferation index and absence of histopathological features of malignancy/atypical adenoma indicate that the parathyroid adenomas arising in these patients did not harbor malignant potential.
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- 2012
19. Evidence of a functional estrogen receptor in parathyroid adenomas
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Ran Ma, Anders Höög, Ming Lu, Mikael Huss, Catharina Larsson, Luqman Sulaiman, Inga Lena Nilsson, Felix Haglund, C. Christofer Juhlin, and Johan Hartman
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Adenoma ,Adult ,Male ,medicine.medical_specialty ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,Diarylpropionitrile ,Clinical Biochemistry ,Estrogen receptor ,Biology ,Biochemistry ,Transcriptome ,chemistry.chemical_compound ,Endocrinology ,Internal medicine ,Cell Line, Tumor ,medicine ,Estrogen Receptor beta ,Humans ,Promoter Regions, Genetic ,Parathyroid adenoma ,Aged ,Aged, 80 and over ,Parathyroid neoplasm ,Biochemistry (medical) ,Estrogen Receptor alpha ,DNA Methylation ,Middle Aged ,medicine.disease ,Gene Expression Regulation, Neoplastic ,Parathyroid Neoplasms ,chemistry ,Receptors, Estrogen ,Estrogen ,CpG Islands ,Female ,Estrogen receptor alpha ,hormones, hormone substitutes, and hormone antagonists ,Primary hyperparathyroidism - Abstract
Primary hyperparathyroidism (PHPT) is most frequently present in postmenopausal women. Although the involvement of estrogen has been suggested, current literature indicates that parathyroid tumors are estrogen receptor (ER) α negative.The aim of the study was to evaluate the expression of ERs and their putative function in parathyroid tumors.A panel of 37 parathyroid tumors was analyzed for expression and promoter methylation of the ESR1 and ESR2 genes as well as expression of the ERα and ERβ1/ERβ2 proteins. Transcriptome changes in primary cultures of parathyroid adenoma cells after treatment with the selective ERβ1 agonist diarylpropionitrile (DPN) and 4-hydroxytamoxifen were identified using next-generation RNA sequencing.Immunohistochemistry revealed very low expression of ERα, whereas all informative tumors expressed ERβ1 (n = 35) and ERβ2 (n = 34). Decreased nuclear staining intensity and mosaic pattern of positive and negative nuclei of ERβ1 were significantly associated with larger tumor size. Tumor ESR2 levels were significantly higher in female vs. male cases. In cultured cells, significantly increased numbers of genes with modified expression were detected after 48 h, compared to 24-h treatments with DPN or 4-hydroxytamoxifen, including the parathyroid-related genes CASR, VDR, JUN, CALR, and ORAI2. Bioinformatic analysis of transcriptome changes after DPN treatment revealed significant enrichment in gene sets coupled to ER activation, and a highly significant similarity to tumor cells undergoing apoptosis.Parathyroid tumors express ERβ1 and ERβ2. Transcriptional changes after ERβ1 activation and correlation to clinical features point to a role of estrogen signaling in parathyroid function and disease.
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- 2012
20. Copy number alterations in small intestinal neuroendocrine tumors determined by array comparative genomic hybridization
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Jamileh Hashemi, Omid Fotouhi, Jan Zedenius, Catharina Larsson, Luqman Sulaiman, Anders Höög, and Magnus Kjellman
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Cancer Research ,DNA Copy Number Variations ,Intestinal Neoplasm ,Array CGH ,Biology ,Neuroendocrine tumors ,Neuroendocrine tumor ,Surgical oncology ,Chromosome 18 ,Intestinal Neoplasms ,medicine ,Genetics ,Cluster Analysis ,Humans ,Neoplasm Metastasis ,Aged ,Aged, 80 and over ,Chromosome Aberrations ,Comparative Genomic Hybridization ,Chromosome Mapping ,Reproducibility of Results ,Small intestine ,Middle Aged ,medicine.disease ,Carcinoid ,Neuroendocrine Tumors ,medicine.anatomical_structure ,Oncology ,Female ,Comparative genomic hybridization ,Research Article - Abstract
Background Small intestinal neuroendocrine tumors (SI-NETs) are typically slow-growing tumors that have metastasized already at the time of diagnosis. The purpose of the present study was to further refine and define regions of recurrent copy number (CN) alterations (CNA) in SI-NETs. Methods Genome-wide CNAs was determined by applying array CGH (a-CGH) on SI-NETs including 18 primary tumors and 12 metastases. Quantitative PCR analysis (qPCR) was used to confirm CNAs detected by a-CGH as well as to detect CNAs in an extended panel of SI-NETs. Unsupervised hierarchical clustering was used to detect tumor groups with similar patterns of chromosomal alterations based on recurrent regions of CN loss or gain. The log rank test was used to calculate overall survival. Mann–Whitney U test or Fisher’s exact test were used to evaluate associations between tumor groups and recurrent CNAs or clinical parameters. Results The most frequent abnormality was loss of chromosome 18 observed in 70% of the cases. CN losses were also frequently found of chromosomes 11 (23%), 16 (20%), and 9 (20%), with regions of recurrent CN loss identified in 11q23.1-qter, 16q12.2-qter, 9pter-p13.2 and 9p13.1-11.2. Gains were most frequently detected in chromosomes 14 (43%), 20 (37%), 4 (27%), and 5 (23%) with recurrent regions of CN gain located to 14q11.2, 14q32.2-32.31, 20pter-p11.21, 20q11.1-11.21, 20q12-qter, 4 and 5. qPCR analysis confirmed most CNAs detected by a-CGH as well as revealed CNAs in an extended panel of SI-NETs. Unsupervised hierarchical clustering of recurrent regions of CNAs revealed two separate tumor groups and 5 chromosomal clusters. Loss of chromosomes 18, 16 and 11 and again of chromosome 20 were found in both tumor groups. Tumor group II was enriched for alterations in chromosome cluster-d, including gain of chromosomes 4, 5, 7, 14 and gain of 20 in chromosome cluster-b. Gain in 20pter-p11.21 was associated with short survival. Statistically significant differences were observed between primary tumors and metastases for loss of 16q and gain of 7. Conclusion Our results revealed recurrent CNAs in several candidate regions with a potential role in SI-NET development. Distinct genetic alterations and pathways are involved in tumorigenesis of SI-NETs.
- Published
- 2013
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