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

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

Authors:	Nguyen, B.; Fong, C.; Luthra, A.; Smith, S. A.; DiNatale, R. G.; Nandakumar, S.; Walch, H.; Chatila, W. K.; Madupuri, R.; Kundra, R.; Bielski, C. M.; Mastrogiacomo, B.; Donoghue, M. T. A.; Boire, A.; Chandarlapaty, S.; Ganesh, K.; Harding, J. J.; Iacobuzio-Donahue, C. A.; Razavi, P.; Reznik, E.; Rudin, C. M.; Zamarin, D.; Abida, W.; Abou-Alfa, G. K.; Aghajanian, C.; Cercek, A.; Chi, P.; Feldman, D.; Ho, A. L.; Iyer, G.; Janjigian, Y. Y.; Morris, M.; Motzer, R. J.; O'Reilly, E. M.; Postow, M. A.; Raj, N. P.; Riely, G. J.; Robson, M. E.; Rosenberg, J. E.; Safonov, A.; Shoushtari, A. N.; Tap, W.; Teo, M. Y.; Varghese, A. M.; Voss, M.; Yaeger, R.; Zauderer, M. G.; Abu-Rustum, N.; Garcia-Aguilar, J.; Bochner, B.; Hakimi, A.; Jarnagin, W. R.; Jones, D. R.; Molena, D.; Morris, L.; Rios-Doria, E.; Russo, P.; Singer, S.; Strong, V. E.; Chakravarty, D.; Ellenson, L. H.; Gopalan, A.; Reis-Filho, J. S.; Weigelt, B.; Ladanyi, M.; Gonen, M.; Shah, S. P.; Massague, J.; Gao, J.; Zehir, A.; Berger, M. F.; Solit, D. B.; Bakhoum, S. F.; Sanchez-Vega, F.; Schultz, N.
Article Title:	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. © 2022 Elsevier Inc.
Keywords:	metastasis; genomics; molecular profiling; mutations; next-generation sequencing; dna sequencing; cancer; pan-cancer; clinical sequencing; organotropism
Journal Title:	Cell
Volume:	185
Issue:	3
ISSN:	0092-8674
Publisher:	Cell Press
Date Published:	2022-02-03
Start Page:	563
End Page:	575.e11
Language:	English
DOI:	10.1016/j.cell.2022.01.003
PUBMED:	35120664
PROVIDER:	scopus
PMCID:	PMC9147702
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85123805833&doi=10.1016%2fj.cell.2022.01.003&partnerID=40&md5=051a338719999875f602d2197cdb930b
Notes:	Article -- Export Date: 1 March 2022 -- Source: Scopus