Dataset Information

Genomic characterization of metastatic patterns from prospective clinical sequencing of 25,000 patients.

ABSTRACT: Metastatic progression is the main cause of death in cancer patients, whereas the underlying genomic mechanisms driving metastasis remain largely unknown. Here, we assembled MSK-MET, a pan-cancer cohort of over 25,000 patients with metastatic diseases. By analyzing genomic and clinical data from this cohort, we identified associations between genomic alterations and patterns of metastatic dissemination across 50 tumor types. We found that chromosomal instability is strongly correlated with metastatic burden in some tumor types, including prostate adenocarcinoma, lung adenocarcinoma, and HR+/HER2+ breast ductal carcinoma, but not in others, including colorectal cancer and high-grade serous ovarian cancer, where copy-number alteration patterns may be established early in tumor development. We also identified somatic alterations associated with metastatic burden and specific target organs. Our data offer a valuable resource for the investigation of the biological basis for metastatic spread and highlight the complex role of chromosomal instability in cancer progression.

SUBMITTER: Nguyen B

PROVIDER: S-EPMC9147702 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genomic characterization of metastatic patterns from prospective clinical sequencing of 25,000 patients.

Nguyen Bastien B Fong Christopher C Luthra Anisha A Smith Shaleigh A SA DiNatale Renzo G RG Nandakumar Subhiksha S Walch Henry H Chatila Walid K WK Madupuri Ramyasree R Kundra Ritika R Bielski Craig M CM Mastrogiacomo Brooke B Donoghue Mark T A MTA Boire Adrienne A Chandarlapaty Sarat S Ganesh Karuna K Harding James J JJ Iacobuzio-Donahue Christine A CA Razavi Pedram P Reznik Ed E Rudin Charles M CM Zamarin Dmitriy D Abida Wassim W Abou-Alfa Ghassan K GK Aghajanian Carol C Cercek Andrea A Chi Ping P Feldman Darren D Ho Alan L AL Iyer Gopakumar G Janjigian Yelena Y YY Morris Michael M Motzer Robert J RJ O'Reilly Eileen M EM Postow Michael A MA Raj Nitya P NP Riely Gregory J GJ Robson Mark E ME Rosenberg Jonathan E JE Safonov Anton A Shoushtari Alexander N AN Tap William W Teo Min Yuen MY Varghese Anna M AM Voss Martin M Yaeger Rona R Zauderer Marjorie G MG Abu-Rustum Nadeem N Garcia-Aguilar Julio J Bochner Bernard B Hakimi Abraham A Jarnagin William R WR Jones David R DR Molena Daniela D Morris Luc L Rios-Doria Eric E Russo Paul P Singer Samuel S Strong Vivian E VE Chakravarty Debyani D Ellenson Lora H LH Gopalan Anuradha A Reis-Filho Jorge S JS Weigelt Britta B Ladanyi Marc M Gonen Mithat M Shah Sohrab P SP Massague Joan J Gao Jianjiong J Zehir Ahmet A Berger Michael F MF Solit David B DB Bakhoum Samuel F SF Sanchez-Vega Francisco F Schultz Nikolaus N

Cell 20220201 3

Metastatic progression is the main cause of death in cancer patients, whereas the underlying genomic mechanisms driving metastasis remain largely unknown. Here, we assembled MSK-MET, a pan-cancer cohort of over 25,000 patients with metastatic diseases. By analyzing genomic and clinical data from this cohort, we identified associations between genomic alterations and patterns of metastatic dissemination across 50 tumor types. We found that chromosomal instability is strongly correlated with metas ...[more]

PMID: 35120664

Similar Datasets

Project description:Although there is a well-known disparity in prostate cancer (PC) incidence and mortality between Chinese and Western patients, the underlying genomic differences have been investigated only sparsely. This clinicogenomic study was conducted to reveal the genomic mutations contributing to the PC disparity across ethnicities and investigate the mutational profile of Chinese PC patients. A total of 1016 Chinese PC patients were prospectively enrolled and subjected to targeted sequencing, resulting in usable sequencing data for 41 genes from 859 patients. Genomic data retrieved from The Cancer Genome Atlas (TCGA; locoregional PC), Memorial Sloan Kettering Cancer Center [MSKCC; metastatic castration-sensitive PC (mCSPC)], and Stand Up To Cancer [SU2C; metastatic castration-resistant PC (mCRPC)] cohorts were used as comparators representing Western men. Genomic mutations were analyzed using an integrated bioinformatic strategy. A comparison of the disease stages revealed that mutations in tumor protein 53 (TP53), androgen receptor (AR), forkhead box A1 (FOXA1), and genes involved in the cell cycle pathway were enriched in mCRPC. Mutations in adenomatous polyposis coli (APC) gene were found to be more prevalent in patients with visceral metastasis. Genomic differences between Western and Chinese men were mainly observed in castration-sensitive PC, with tumors from Chinese men having more FOXA1 (11.4% vs. 4.2%) but fewer TP53 (4.8% vs. 13%) mutations in locoregional PC and harboring fewer TP53 (11% vs. 29.2%), phosphatase and tensin homolog (PTEN; 2.5% vs. 10.3%), and APC (1.7% vs. 7.4%) mutations in the mCSPC stage than those of Western men. Patients of both ethnicities with mCRPC had similar mutational spectra. Furthermore, FOXA1 class-2 was less common than FOXA1 class-1 and showed no enrichment in metastasis, contrary to the findings in the Western cohort. Our study provides a valuable resource for a better understanding of PC in China and reveals the genomic alterations associated with PC disparity across races.

Dataset Information

Genomic characterization of metastatic patterns from prospective clinical sequencing of 25,000 patients.

Publications

Genomic characterization of metastatic patterns from prospective clinical sequencing of 25,000 patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets