Project description:Ovarian cancer is characterized by multiple structural aberrations; most are passenger alterations which do not confer tumor growth. Like many cancers, it is a heterogeneous disease and till date, the histotype-specific copy number landscape has been difficult to elucidate. To dissect the heterogeneity of ovarian cancer and understand the pathogenesis of its various histotypes, we developed an in silico hypothesis-driven workflow to identify histotype-specific copy number aberrations across multiple datasets of epithelial ovarian cancer. In concordance with previous studies on global copy number changes, our study showed similar alterations. However, when the landscape was de-convoluted into histotypes, distinct alterations were observed. We report here a comprehensive histotype-specific copy number landscape of ovarian cancer and showed that there is genomic diversity between the histotypes; some involving well known cancer genes and some novel potential driver genes. Besides preferential occurrence of alterations in some histotypes, opposite trends of alteration were observed; such as ERBB2 amplification in mucinous but deletion in serous tumors. The landscape highlights the need for identifying histotype-specific aberrations in ovarian cancer and present potential to tailor management of ovarian cancer based on molecular signature of histotypes. 56 samples containing the 4 histotypes were used for this study. It contained 12 clear cell carcinoma, 6 endometrioid adenocarcinoma, 2 mucinous adenocarcinoma, 5 mucinous-borderline tumors, 26 serous adenocarcinoma, and 5 serous-borderline tumors.
Project description:Ovarian cancer is characterized by multiple structural aberrations; most are passenger alterations which do not confer tumor growth. Like many cancers, it is a heterogeneous disease and till date, the histotype-specific copy number landscape has been difficult to elucidate. To dissect the heterogeneity of ovarian cancer and understand the pathogenesis of its various histotypes, we developed an in silico hypothesis-driven workflow to identify histotype-specific copy number aberrations across multiple datasets of epithelial ovarian cancer. In concordance with previous studies on global copy number changes, our study showed similar alterations. However, when the landscape was de-convoluted into histotypes, distinct alterations were observed. We report here a comprehensive histotype-specific copy number landscape of ovarian cancer and showed that there is genomic diversity between the histotypes; some involving well known cancer genes and some novel potential driver genes. Besides preferential occurrence of alterations in some histotypes, opposite trends of alteration were observed; such as ERBB2 amplification in mucinous but deletion in serous tumors. The landscape highlights the need for identifying histotype-specific aberrations in ovarian cancer and present potential to tailor management of ovarian cancer based on molecular signature of histotypes. 56 samples containing the 4 histotypes were used for this study. It contained 12 clear cell carcinoma, 6 endometrioid adenocarcinoma, 2 mucinous adenocarcinoma, 5 mucinous-borderline tumors, 26 serous adenocarcinoma, and 5 serous-borderline tumors. Data was pre-processed and normalized with Hapmap JPT using the Affymetric Genotyping Console.
Project description:Intra-individual tumoral heterogeneity (ITH) is a hallmark of solid tumors and impedes accurate genomic diagnosis and selection of proper therapy. The purpose of this study was to identify ITH of ovarian serous adenocarcinomas (OSAs) and to determine the utility of ascitic cancer cells as a resource for mutation profiling in spite of ITH. We performed whole-exome sequencing, copy number profiling, and DNA methylation profiling of four OSA genomes using multiregional biopsies from 13 intraovarian lesions, 12 extraovarian tumor lesions (omentum/peritoneum), and ascitic cells. We observed substantial levels of heterogeneity in mutations and copy number alterations (CNAs) of the OSAs. We categorized the mutations into 'common', 'shared' and 'private' according to the regional distribution. Six common, 8 shared, and 24 private mutations were observed in known cancer-related genes,. but common mutations had a higher mutant allele frequency and included TP53 mutations in all four OSAs. Region-specific chromosomal amplifications and deletions involving BRCA1, PIK3CA, and RB1 were also identified. Of note, the mutations detected in ascitic cancer cells represented 92.3-100% of overall somatic mutations in the given case. Phylogenetic analyses of ascitic genomes predicted a polyseeding origin of somatic mutations in ascitic cells. Our results demonstrate that despite ITH, somatic mutations, CNAs, and DNA methylations in both âcommonâ category and cancer-related genes were highly conserved in ascitic cells of OSAs, highlighting the clinical relevance of genome analysis of ascitic cells. Ascitic tumor cells may serve as a potential resource to discover somatic mutations of primary OSA with diagnostic and therapeutic relevance. The purpose of this study was to identify intra-individual tumor heterogenety of ovarian serous adenocarcinomas Four to nine different ovarian cancer areas from intraovarian and extra-ovarian lesions that were at least 1cm apart as well as 50 ml ascites were collected from the four OSA patients. Genomic DNA from tumor and matched normal samples were simultaneously hybridized onto the array. Total 29 array experiments were conducted.
Project description:Multi-region whole genome sequencing of an high grade serous ovarian carcinoma sample for characterization of genomic intra-tumoural heterogeneity.
Project description:41 lung adenocarcinoma from never-smokers hybridized on Illumina SNP arrays on 13 HumanCNV370-Quadv3 chips. High-resolution array comparative genomic hybridization analysis of lung adenocarcinoma in 41 never smokers for identification of new minimal common regions (MCR) of gain or loss. The SNP array analysis validated copy-number aberrations and revealed that RB1 and WRN were altered by recurrent copy-neutral loss of heterozygosity.The present study has uncovered new aberrations containing cancer genes. The oncogene FUS is a candidate gene in the 16p region that is frequently gained in never smokers. Multiple genetic pathways defined by gains of MYC, deletions of RB1 and WRN or gains on 7p and 7q are involved in lung adenocarcinoma in never smokers. A 'Cartes d'Identite des Tumeurs' (CIT) project from the French National League Against Cancer (http://cit.ligue-cancer.net) 41 samples hybridized on Illumina SNP arrays. Submitter : Fabien PETEL petelf@ligue-cancer.net . Project leader : Pr Pierre FOURET pierre.fouret@psl.aphp.fr
Project description:Molecular analysis of high-grade serous ovarian carcinoma with and without associated serous tubal intra-epithelial carcinoma [CNV]