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

Authors :
Charles M. Rudin
Brooke Mastrogiacomo
Bastien Nguyen
Julio Garcia-Aguilar
Ahmet Zehir
Christopher J. Fong
Ramyasree Madupuri
Eric Rios-Doria
Joan Massagué
Rona Yaeger
Nadeem R. Abu-Rustum
Carol Aghajanian
Ed Reznik
Eileen M. O'Reilly
Nikolaus Schultz
Subhiksha Nandakumar
Michael A. Postow
Christine A. lacobuzio-Donahue
Luc G. T. Morris
Darren R. Feldman
Robert J. Motzer
Pedram Razavi
Ghassan K. Abou-Alfa
Mithat Gonen
William R. Jarnagin
Michael J. Morris
Vivian E. Strong
Sarat Chandarlapaty
Michael F. Berger
William D. Tap
Andrea Cercek
Nitya Raj
Alan L. Ho
Min Yuen Teo
James J. Harding
Adrienne Boire
Lora H. Ellenson
Bernard H. Bochner
Sohrab P. Shah
Anna M. Varghese
Craig M. Bielski
Wassim Abida
Jonathan E. Rosenberg
David B. Solit
Anton Safonov
Ritika Kundra
Henry Walch
Renzo G. DiNatale
Martin H. Voss
Francisco Sanchez-Vega
David R. Jones
Alexander N. Shoushtari
Shaleigh A. Smith
Samuel Singer
Mark E. Robson
Karuna Ganesh
Anisha Luthra
Debyani Chakravarty
Jianjiong Gao
Britta Weigelt
Dmitriy Zamarin
A.A. Hakimi
Yelena Y. Janjigian
Daniela Molena
Marc Ladanyi
Walid K. Chatila
Gregory J. Riely
Jorge S. Reis-Filho
Samuel F. Bakhoum
Gopakumar Iyer
Marjorie G. Zauderer
Paul Russo
Anuradha Gopalan
Ping Chi
Publication Year :
2021
Publisher :
Cold Spring Harbor Laboratory, 2021.

Abstract

Progression to metastatic disease remains the main cause of cancer death. Yet, the underlying genomic mechanisms driving metastasis remain largely unknown. Here, we present MSK-MET, an integrated pan-cancer cohort of tumor genomic and clinical outcome data from more than 25,000 patients. We analyzed this dataset to identify associations between tumor 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-positive breast ductal carcinoma, but not in others, such as colorectal adenocarcinoma, pancreatic adenocarcinoma and high-grade serous ovarian cancer. We also identified specific somatic alterations associated with increased metastatic burden and specific routes of metastatic spread. Our data offer a unique resource for the investigation of the biological basis for metastatic spread and highlight the crucial role of chromosomal instability in cancer progression.

Details

Database :
OpenAIRE
Accession number :
edsair.doi...........3aa1b9ce54d8f629cd11c48bb6cc6c90
Full Text :
https://doi.org/10.1101/2021.06.28.450217