Search

Optimal selection of high-risk patients with stage II colon cancer is crucial to ensure clinical benefit of adjuvant chemotherapy. Here, we investigated the prognostic value of genomic intratumor heterogeneity and aneuploidy for disease recurrence. We combined targeted sequencing, SNP arrays, fluorescence in situ hybridization, and immunohistochemistry on a retrospective cohort of 84 untreated stage II colon cancer patients. We assessed the clonality of copy-number alterations (CNAs) and mutations, CD8

IntroducciónLa punción aspiración con aguja fina (PAAF) constituye un arma diagnóstica valiosa para filiar las masas cervicales.Material y métodosRealizamos un estudio retrospectivo de las PAAF solicitadas entre 2012 y 2018. Recogimos datos de localización de la masa, la utilización de ecografía como guía de la punción, la realización de biopsia abierta y los resultados anatomopatológicos de la punción y de la biopsia abierta.ResultadosSe realizaron 93 PAAF, resultando 43 punciones no diagnósticas (46%). 38 PAAF (41%) resultaron benignas y 12 (13%) malignas. Se utilizó ecografía como guía en 41 punciones, siendo 35 diagnósticas (85%). En los casos en los que no se usó ecografía el 31% obtuvieron un diagnóstico.En 21 casos (23%) se realizó biopsia abierta para confirmación histopatológica. Las localizaciones más frecuentes fueron área II (43%) y parótida (48%). En 16 pacientes (76%) el resultado definitivo fue benigno y en 5 (24%) maligno. La sensibilidad fue 86%, la especificidad 100%, el valor predictivo positivo 100%, el valor predictivo negativo 94% y la precisión diagnóstica 95%. Atendiendo a la guía con ecografía, la sensibilidad, especificidad, valor predictivo positivo y valor predictivo negativo fueron 100%. Los diagnósticos histopatológicos más frecuentes fueron adenoma pleomorfo (33%), quiste branquial (24%) y carcinoma epidermoide (24%).DiscusiónNuestro porcentaje de punciones diagnósticas es ligeramente superior al 50%, obteniendo mayor éxito (85%) si es ecoguiada. La sensibilidad, especificidad, valor predictivo positivo y negativo son similares a los encontrados en la literatura, siendo superior el porcentaje de PAAF no diagnósticas en nuestro centro.

ResumenIntroducción y objetivo: La sialoadenosis, también denominada sialosis, consiste en una patología benigna, degenerativa de las glándulas salivares mayores, provocando un agrandamiento difuso de las mismas.Material y método: Presentamos el caso de una paciente con esta patología poco común.Resultados: Su etiología se asocia a consumo de alcohol, trastornos alimentarios o enfermedades sistémicas (diabetes, acromegalia o hipotiroidismo). También puede estar provocada como efecto adverso de algunos fármacos.Conclusión: El tratamiento debe ser etiológico en la medida que sea posible, reservando el tratamiento quirúrgico para los casos en los que la alteración estética sea inaceptable. Palabras claveSialosis, glándulas parótias, agrandamiento difuso. SummaryIntroduction and objective: The sialoadenosis, also called sialosis, consists of a benign, degenerative pathology of the major salivary glands, causing a diffuse enlargement of them. Material and method: We present the case of a patient with this uncommon pathology. Results: Its etiology is associated with alcohol consumption, eating disorders or systemic diseases (diabetes, acromegaly or hypothyroidism). It can also be caused as an adverse effect of some drugs. Conclusions: The treatment must be etiological, reserving surgical treatment for cases in which the aesthetic alteration is unacceptable. KeywordsSialosis, Parotid glands, difusse enlargement.

Complex chromosome rearrangements (CCRs) are unusual structural chromosome alterations found in humans, and to date only a few have been characterized molecularly. New mechanisms, such as chromothripsis, have been proposed to explain the presence of the CCRs in cancer cells and in patients with congenital disorders and/or mental retardation. The aim of the present study was the molecular characterization of a constitutional CCR in a girl with multiple congenital disorders and intellectual disability in order to determine the genotype-phenotype relation and to clarify whether the CCR could have been caused by chromosomal catastrophic events. The present CCR was characterized by G-banding, high-resolution CGH, multiplex ligation-dependent probe amplification and subtelomeric 2q-FISH analyses. Preliminary results indicate that the de novo CCR is unbalanced showing a 2q37.3 deletion and 2q34q37.2 partial trisomy. Our patient shows some of the typical traits and intellectual disability described in patients with 2q37 deletion and also in carriers of 2q34q37.2 partial trisomy; thus, the clinical disorders could be explained by additional effects of both chromosome alterations (deletions and duplications). A posterior, sequential FISH study using BAC probes revealed the unexpected presence of at least 17 different reorganizations affecting 2q34q37.2, suggesting the existence of chromosome instability in this region. The present CCR is the first case described in the literature of heterogeneity of unbalanced CCRs affecting a small region of 2q, indicating that the mechanisms involved in constitutional chromosome rearrangement may be more complex than previously thought.

Seminal plasma proteomics studies could represent a new approach for the determination of molecular elements driving male infertility, resulting in a better male infertility characterization. The aim of this study is to investigate proteomic differences in seminal plasma samples from fertile and infertile individuals. For that, semen samples were selected according to semen analysis, clinical pathology, and values of sperm DNA fragmentation (alkaline and neutral Comet assay and Sperm Chromatin Dispersion test). A total of 24 seminal plasma samples classified in four groups were processed: fertile donors (FD), recurrent miscarriage patients (RM), asthenoteratozoospermic patients (ATZ), and asthenoteratozoospermic patients with varicocele (ATZ-VAR). Results obtained by 2D-differential gel electrophoresis (2D-DIGE) revealed 26 spots significantly increased in fertile donors when compared to patient groups. Also, eight spots in the ATZ group and two in the ATZ-VAR group were decreased compared to the other groups. Twenty-eight proteins were identified by mass spectrometry (MS), most of them involved in metabolic and cellular processes and with a catalytic or binding function. Protein&ndash, protein interactions through Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) tool suggest that a large part of them were associated with each other. Furthermore, most of them were associated with ubiquitin C, indicating that it could play an important regulation role, resulting in a potential male infertility biomarker.

In families at risk from monogenic diseases affected offspring, it is fundamental the development of a suitable Double Factor Preimplantation Genetic Testing (DF-PGT) method for both single-gene analysis and chromosome complement screening. Aneuploidy is not only a major issue in advanced-maternal-age patients and balanced translocation carriers, but also the aneuploidy rate is extremely high in patients undergoing in vitro fertilization (IVF), even in young donors. To adequate NGS technology to the DF-PGT strategy four different whole genome amplification systems (Sureplex, MALBAC, and two multiple displacement amplification systems-MDA) were tested using TruSight One panel on cell lines and blastocyst trophectoderm biopsies-TE. Embryo cytogenetic status was analyzed by Nexus software. Sureplex and MALBAC DNA products were considered not suitable for PGT diagnosis due to inconsistent and poor results on Trusight one (TSO) panel. Results obtained with both MDA based methods (GEH-MDA and RG-MDA) were appropriate for direct mutation detection by TSO NGS platform. Nevertheless, RG-MDA amplification products showed better coverage and lower ADO rates than GEH-MDA. The present work also demonstrates that the same TSO sequencing data is suitable not only for the direct mutation detection, but also for the indirect mutation detection by linkage analysis of informative SNPs. The present work also demonstrates that Nexus software is competent for the detection of CNV by using with TSO sequencing data from RG-MDA products, allowing for the whole cytogenetic characterization of the embryos. In conclusion, successfully development of an innovative and promising DF-PGT strategy using TSO-NGS technology in TE biopsies, performed in-house in a single laboratory experience, has been done in the present work. Additional studies should be performed before it could be used as a diagnostic alternative in order to validate this approach for the detection of chromosomal aneuploidies.

Objective Enhancing implantation rates in preimplantation genetic diagnosis (PGD) cycles is still a challenging aspect to address. As aneuploidy can be one of the factors influencing the low implantation rates obtained, the aim of this work was to combine monogenic analysis with comprehensive aneuploidy screening (double factor) in order to transfer the selected (healthy and euploid) embryos in the same in-vitro fertilization (IVF) cycle. Method In the present double-factor PGD (DF-PGD) approach, a single blastomere was biopsied from each embryo, and the whole genome amplification DNA product obtained was successfully used for both monogenic analysis and metaphase comparative genomic hybridization cytogenetic screening. The developed DF-PGD was applied to 62 embryos from seven families at risk for monogenic-inherited diseases in a total of seven IVF-DF-PGD cycles. Results While 68.2% of the diagnosed embryos were healthy for the monogenic diseases, only 43.3% of them were chromosomally normal considering aneuploidies and/or segmental chromosome imbalances. Six out of seven families had transferrable embryos according to DF-PGD results. Two healthy babies were born from the 11 selected embryo transfers. Conclusion In families at risk for monogenic diseases, the DF-PGD is a useful tool to select healthy and potentially viable embryos for transfer, according to their chromosome complement. © 2015 John Wiley & Sons, Ltd.

In this article we describe and build a model of a historical weighing device proposed by the Spanish engineer Dario Bacas in the second half of the 19th century. The balance was named 'goniobarimeter' by its inventor, and the weighing principle is based on a curious, and not very well known, property of the cycloid. The simplicity of the design makes it especially suitable for a hands-on educational project with pre-university physics students.

OBJECTIVES To classify bladder tumors according to their genomic imbalances and evaluate their association with patient's outcome. METHODS Sixty-three superficially and minimally invasive bladder tumors were analyzed by conventional comparative genomic hybridization. Subtelomeric screening in 15 of these tumors was performed by multiplex ligation-dependent probe amplification. RESULTS Losses of 9q and 9p (32% and 25% of all cases, respectively) as well as gains of chromosomes Xq and Xp (28% and 25%, respectively) were the most frequent chromosome imbalances. Losses of 8p and gains in 1q and 8q were detected in >20% of cases. Tumors were classified into 3 groups according to their individualized pattern of gains and losses. The largest group was characterized by few chromosome imbalances, presenting 77% and 49% of the Ta and T1 tumors, respectively. Another group characterized by chromosomal gains, was composed of equal number of Ta and T1 tumors, with +1q and +17q gains being the most common imbalances. A minority group was characterized by chromosomal losses on 11q, 5q, and 6q. The multiplex ligation-dependent probe amplification study showed good correlation with comparative genomic hybridization results. With regard to the biological significance of this classification, a remarkable fact is that this minority group composed mainly of T1 tumors, showed a significant decrease in patient overall survival. CONCLUSIONS Our data suggest that superficial carcinomas of the bladder can be subdivided into a larger number of subclasses than had previously been expected. Our results also demonstrate a decreased survival among patients whose tumors show more genomic losses than gains. UROLOGY 75: 347-356, 2010. Crown Copyright (C) 2010 Published by Elsevier Inc.

Study Type – Prognosis (case series) Level of Evidence 4 OBJECTIVE To estimate the relative risk of developing a second primary neoplasm, in particular lung cancer, after having non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS Patients were included in the study if they had developed NMIBC between 1995 and 2003. All clinical data were extracted from the medical records of our institution’s database. The interval between neoplasms, smoking habits, histological subtypes and survival were also analysed. Patient follow-up was ≥5 years. RESULTS We found 231 patients with NMIBC, 39 of which had a second primary neoplasm: 10 lung cancer, one pancreas, one gastric, one pharynx, one liver, one parathyroid, one oesophageal, five basal cell carcinoma, three larynx, two colon, three rectal and 10 prostate. In patients with lung cancer, NMIBC was the first primary tumour. Overall, the median (range) interval between occurrence of NMIBC and lung cancer was 54.2 (8–168) months. For the relationship between the observed and expected cases of lung cancer, after normalizing our frequencies to the sex ratio and age of our group of patients, the risk of lung cancer was 10.27-fold higher in patients with NMIBC as compared with the general population of Catalonia (95% confidence interval 4.92–18.88). CONCLUSION We consider that an annual examination for the detection and prevention of lung cancer must be included in clinical guides for patients with NMIBC. This proposal is reinforced by the finding that death in our group of patients with both tumours was always derived from lung cancer and not from bladder cancer.

Colorectal cancer (CRC) is characterized by specific patterns of copy number alterations (CNAs), which helped with the identification of driver oncogenes and tumor suppressor genes (TSGs). More recently, the usage of single nucleotide polymorphism arrays provided information of copy number neutral loss of heterozygosity, thus suggesting the occurrence of somatic uniparental disomy (UPD) and uniparental polysomy (UPP) events. The aim of this study is to establish an integrative profiling of recurrent UPDs/UPPs and CNAs in sporadic CRC. Our results indicate that regions showing high frequencies of UPD/UPP mostly coincide with regions typically involved in genomic losses. Among them, chromosome arms 3p, 5q, 9q, 10q, 14q, 17p, 17q, 20p, 21q and 22q preferentially showed UPDs/UPPs over genomic losses suggesting that tumor cells must maintain the disomic state of certain genes to favor cellular fitness. A meta-analysis using over 300 samples from The Cancer Genome Atlas confirmed our findings. Several regions affected by recurrent UPDs/UPPs contain well-known TSGs, as well as novel candidates such as ARID1A, DLC1, TCF7L2 and DMBT1. In addition, VCAN, FLT4, SFRP1 and GAS7 were also frequently involved in regions of UPD/UPP and displayed high levels of methylation. Finally, sequencing and fluorescence in situ hybridization analysis of the gene APC underlined that a somatic UPD event might represent the second hit to achieve biallelic inactivation of this TSG in colorectal tumors. In summary, our data define a profile of somatic UPDs/UPPs in sporadic CRC and highlights the importance of these events as a mechanism to achieve the inactivation of TSGs.

Enhancing implantation rates in preimplantation genetic diagnosis (PGD) cycles is still a challenging aspect to address. As aneuploidy can be one of the factors influencing the low implantation rates obtained, the aim of this work was to combine monogenic analysis with comprehensive aneuploidy screening (double factor) in order to transfer the selected (healthy and euploid) embryos in the same in-vitro fertilization (IVF) cycle.In the present double-factor PGD (DF-PGD) approach, a single blastomere was biopsied from each embryo, and the whole genome amplification DNA product obtained was successfully used for both monogenic analysis and metaphase comparative genomic hybridization cytogenetic screening. The developed DF-PGD was applied to 62 embryos from seven families at risk for monogenic-inherited diseases in a total of seven IVF-DF-PGD cycles.While 68.2% of the diagnosed embryos were healthy for the monogenic diseases, only 43.3% of them were chromosomally normal considering aneuploidies and/or segmental chromosome imbalances. Six out of seven families had transferrable embryos according to DF-PGD results. Two healthy babies were born from the 11 selected embryo transfers.In families at risk for monogenic diseases, the DF-PGD is a useful tool to select healthy and potentially viable embryos for transfer, according to their chromosome complement.

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.

Altres ajuts: Predoctoral grant from the Universitat Autònoma de Barcelona Comprehensive chromosome analysis techniques such as metaphase-Comparative Genomic Hybridisation (CGH) and array-CGH are available for single-cell analysis. However, while metaphase-CGH and BAC array-CGH have been widely used for Preimplantation Genetic Diagnosis, oligonucleotide array-CGH has not been used in an extensive way. A comparison between oligonucleotide array-CGH and metaphase-CGH has been performed analysing 15 single fibroblasts from aneuploid cell-lines and 18 single blastomeres from human cleavage-stage embryos. Afterwards, oligonucleotide array-CGH and BAC array-CGH were also compared analysing 16 single blastomeres from human cleavage-stage embryos. All three comprehensive analysis techniques provided broadly similar cytogenetic profiles; however, non-identical profiles appeared when extensive aneuploidies were present in a cell. Both array techniques provided an optimised analysis procedure and a higher resolution than metaphase-CGH. Moreover, oligonucleotide array-CGH was able to define extra segmental imbalances in 14.7% of the blastomeres and it better determined the specific unbalanced chromosome regions due to a higher resolution of the technique (≈20 kb). Applicability of oligonucleotide array-CGH for Preimplantation Genetic Diagnosis has been demonstrated in two cases of Robertsonian translocation carriers 45,XY,der(13;14)(q10;q10). Transfer of euploid embryos was performed in both cases and pregnancy was achieved by one of the couples. This is the first time that an oligonucleotide array-CGH approach has been successfully applied to Preimplantation Genetic Diagnosis for balanced chromosome rearrangement carriers.

Aneuploidy has been a major issue in human gametes and is closely related to fertility problems, as it is known to be present in cleavage stage embryos and gestational losses. Pre-meiotic chromosome abnormalities in women have been previously described. The aim of this study is to assess the whole-chromosome complement in immature oocytes to find those abnormalities caused by mitotic instability. For this purpose, a total of 157 oocytes at the germinal vesicle or metaphase I stage, and discarded from IVF cycles, were analysed by CGH. Fifty-six women, between 18 and 45 years old (mean 32.5 years), including 32 IVF patients (25–45 years of age) and 24 IVF oocyte donors (18–33 years of age), were included in the study. A total of 25/157 (15.9%) of the oocytes analysed, obtained from three IVF clinics, contained chromosome abnormalities, including both aneuploidy (24/157) and structural aberrations (9/157). Independently of the maternal age, the incidence of abnormal oocytes which originated before meiosis is 15.9%, and these imbalances were found in 33.9% of the females studied. This work sheds light on the relevance of mitotic instability responsible for the generation of the abnormalities present in human oocytes.

Background Aneuploidy, centrosome abnormalities and gene amplification are hallmarks of chromosome instability (CIN) in cancer. Yet there are no studies of the in vivo behavior of these phenomena within the same bladder tumor. Methods Twenty-one paraffin-embedded bladder tumors were analyzed by conventional comparative genome hybridization and fluorescence in situ hybridization (FISH) with a cyclin D1 gene (CCND1)/centromere 11 dual-color probe. Immunofluorescent staining of α, β and γ tubulin was also performed. Results Based on the CIN index, defined as the percentage of cells not displaying the modal number for chromosome 11, tumors were classified as CIN-negative and CIN-positive. Fourteen out of 21 tumors were considered CIN-positive. All T1G3 tumors were included in the CIN-positive group whereas the majority of Ta samples were classified as CIN-negative tumors. Centrosome clustering was observed in six out of 12 CIN-positive tumors analyzed. CCND1 amplification in homogeneously staining regions was present in six out of 14 CIN-positive tumors; three of them also showed amplification of this gene in double minutes. Conclusions Complex in vivo behavior of CCND1 amplicon in bladder tumor cells has been demonstrated by accurate FISH analysis on paraffin-embedded tumors. Positive correlation between high heterogeneity, centrosome abnormalities and CCND1 amplification was found in T1G3 bladder carcinomas. This is the first study to provide insights into the coexistence of CCND1 amplification in homogeneously staining regions and double minutes in primary bladder tumors. It is noteworthy that those patients whose tumors showed double minutes had a significantly shorter overall survival rate (p < 0.001).

Prognosis (case series) Level of Evidence 4.To estimate the relative risk of developing a second primary neoplasm, in particular lung cancer, after having non-muscle-invasive bladder cancer (NMIBC).Patients were included in the study if they had developed NMIBC between 1995 and 2003. All clinical data were extracted from the medical records of our institution's database. The interval between neoplasms, smoking habits, histological subtypes and survival were also analysed. Patient follow-up wasor=5 years.We found 231 patients with NMIBC, 39 of which had a second primary neoplasm: 10 lung cancer, one pancreas, one gastric, one pharynx, one liver, one parathyroid, one oesophageal, five basal cell carcinoma, three larynx, two colon, three rectal and 10 prostate. In patients with lung cancer, NMIBC was the first primary tumour. Overall, the median (range) interval between occurrence of NMIBC and lung cancer was 54.2 (8-168) months. For the relationship between the observed and expected cases of lung cancer, after normalizing our frequencies to the sex ratio and age of our group of patients, the risk of lung cancer was 10.27-fold higher in patients with NMIBC as compared with the general population of Catalonia (95% confidence interval 4.92-18.88).We consider that an annual examination for the detection and prevention of lung cancer must be included in clinical guides for patients with NMIBC. This proposal is reinforced by the finding that death in our group of patients with both tumours was always derived from lung cancer and not from bladder cancer.

Cuando una tecnología irrumpe en el ámbito de una cultura no se limita a cumplir las tareas obvias asociadas a su función: modifica la realidad del usuario, y al usuario también. Ciberespacio, cultura y sociedad son palabras que suponen una interpelación, ante la que los académicos tenemos que generar respuestas que nos permitan comprender su realidad, y explicarla a nuestros lectores When a particular form of technology materializes in the environs of a culture, it accomplishes far more than the obvious tasks associated with its function. It modifies the user's world as well as the user. Cyberspace, culture and society are words that raise questions academics are called on to answer in a way that enables us to understand the reality of cyberspace and to explain it to our readers

Comparative genomic hybridization and fluorescence in situ hybridization were used to define genetic changes associated with multifocal bladder cancer and to investigate whether the genetic relationship between synchronous urothelial tumors is similar to that observed within different parts of the same tumor. We investigated 8 synchronous urothelial tumors from 3 patients and macroscopically different parts of the same tumor from 2 other patients. The most frequent imbalances were gains of 1q, 2p, and 17q, and losses in 4q. The high number of chromosome imbalances detected in the present report confirms that a high level of chromosome instability could be character- istic of multicentric bladder tumors. Comparative genomic hybridization profiles obtained from independent tumors belonging to the same patient allowed us to elaborate cytogenetic pedigrees portraying the accumulation of chromo- some alterations as a form of clonal evolution from a single precursor cell. The analysis of different macroscopic parts of the same tumor allowed us to detect chromosomal heterogeneity and to delineate intratumor clonal evolution. Some chromo- some regions that appeared as a gain in one subpopulation were amplified in others indicating a genetic evolution process. Identical processes were observed in different tumors of the same patient. Expansion of chromosome gains and losses between different parts of the same tumor as well as in different tumors of the same patient was also observed. Our results not only provide further evidence of a clonal relationship between different synchronous bladder tumors but also show that the intratumor heterogeneity present in different subpopulations of the same tumor reproduces the behavior of independent synchronous tumors in a same patient.

Objective: To assess whether preimplantation genetic screening can successfully identify cytogenetically normal embryos in couples carrying balanced chromosome rearrangements in addition to increased sperm DNA fragmentation. Design: Comprehensive preimplantation genetic screening was performed on three couples carrying chromosome rearrangements. Sperm DNA fragmentation was assessed for each patient. Setting: Academic center. Patient(s): One couple with the male partner carrying a chromosome 2 pericentric inversion and two couples with the male partners carrying a Robertsonian translocation (13:14 and 14:21, respectively). Intervention(s): A single blastomere from each of the 18 cleavage-stage embryos obtained was analysed by metaphase comparative genomic hybridization. Single-and double-strand sperm DNA fragmentation was determined by the alkaline and neutral Comet assays. Main Outcome Measure(s): Single-and double-strand sperm DNA fragmentation values and incidence of chromosome imbalances in the blastomeres were analyzed. Result(s): The obtained values of single-strand sperm DNA fragmentation were between 47% and 59%, and the double-strand sperm DNA fragmentation values were between 43% and 54%. No euploid embryos were observed in the couple showing the highest single-strand sperm DNA fragmentation. However, euploid embryos were observed in the other two couples: embryo transfer was performed, and pregnancy was achieved by the couple showing the lowest sperm DNA fragmentation values. Conclusion(s): Preimplantation genetic screening enables the detection of euploid embryos in couples affected by balanced chromosome rearrangements and increased sperm DNA fragmentation. Even though sperm DNA fragmentation may potentially have clinical consequences on fertility, comprehensive preimplantation genetic screening allows for the identification and transfer of euploid embryos. (C) 2015 by American Society for Reproductive Medicine.

Mantle-cell lymphoma (MCL) is genetically characterized by 11q13 chromosomal translocations involving the CCND1 gene. We have characterized five MCL cell lines, JVM-2, GRANTA-519, REC-1, JEKO-1, and NCEB-1, combining metaphase and array comparative genomic hybridization, multicolor-FISH, and molecular analysis. Our results revealed common gained regions at 2p14, 9q31.2–qter, 11q13.1–q21, 13q14–q21.2, 13q34–qter and 18q21.1–q22.1, and losses at 1p21.2–p31.1, 2p11.2, 8p21.2–pter, 9p21.3–pter, 11q23.3–qter, 17p11.2–pter, and 17q21.2–q22.2. All cell lines except JVM-2, displayed moderate or high numerical chromosome instability. In addition, an ongoing level of chromosome rearrangements was observed in REC-1. Surprisingly, NCEB-1 carried several stable mouse chromosomes and showed expression of both human and murine bcl-2 protein. Our findings indicate that these cell lines represent three patterns of chromosome evolution in MCL and may be useful to understand the pathogenesis of this neoplasm. © 2005 Elsevier Ltd. All rights reserved.

Objective To investigate if there is an association between single-cell replicative stage and the segmental chromosome imbalances detected by comparative genomic hybridization (CGH). Design First, 135 fibroblasts from cell-line GM03184 (Coriell) at three cell stages (G0/G1, S, and G2/M) were amplified by degenerate oligonucleotide–primed polymerase chain reaction (DOP-PCR) or Sureplex and blindly analyzed by CGH. Second, 85 human blastomeres at the interphase and the metaphase stages, from 30 donated human cryopreserved embryos, were amplified by Sureplex and analyzed by CGH. Setting Academic center for reproductive medicine. Patient(s) None. Intervention(s) None. Main Outcome Measure(s) Incidence of aneuploidy and segmental imbalances detected at the different cell stages. Result(s) In DOP-PCR amplifications of fibroblasts, an increased incidence of segmental abnormalities was detected in the S phase. In Sureplex amplifications of fibroblasts and blastomeres, no differences were detected between the different cell stages. A significantly increased incidence of structural abnormalities was seen in the aneuploid blastomeres. Conclusion(s) The segmental imbalances detected after Sureplex amplification in 73.3% of the cryopreserved embryos analyzed are mainly nontransitory. They correspond to segmental imbalances present in the cells due to chromosome instability, rather than to replicative DNA segments.

Background Transcriptional profiling of prostate cancer (PC) has unveiled new markers of neoplasia and allowed insights into mechanisms underlying this disease. Genomewide analyses have also identified new chromosomal abnormalities associated with PC. The combination of both classes of data for the same sample cohort might provide better criteria for identifying relevant factors involved in neoplasia. Here we describe transcriptional signatures identifying distinct normal and tumoral prostate tissue compartments, and the inference and demonstration of a new, highly recurrent copy number gain on chromosome 17q25.3. Methods We have applied transcriptional profiling to tumoral and non-tumoral prostate samples with relatively homogeneous epithelial representations as well as pure stromal tissue from peripheral prostate and cultured cell lines, followed by quantitative RT-PCR validations and immunohistochemical analysis. In addition, we have performed in silico colocalization analysis of co-regulated genes and validation by fluorescent in situ hybridization (FISH). Results The transcriptomic analysis has allowed us to identify signatures corresponding to non-tumoral luminal and tumoral epithelium, basal epithelial cells, and prostate stromal tissue. In addition, in silico analysis of co-regulated expression of physically linked genes has allowed us to predict the occurrence of a copy number gain at chromosomal region 17q25.3. This computational inference was validated by fluorescent in situ hybridization, which showed gains in this region in over 65% of primary and metastatic tumoral samples. Conclusion Our approach permits to directly link gene copy number variations with transcript co-regulation in association with neoplastic states. Therefore, transcriptomic studies of carefully selected samples can unveil new diagnostic markers and transcriptional signatures highly specific of PC, and lead to the discovery of novel genomic abnormalities that may provide additional insights into the causes and mechanisms of prostate cancer.