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Whole-genome characterization of lung adenocarcinomas lacking the RTK/RAS/RAF pathway.
Carrot-Zhang, Jian; Yao, Xiaotong; Devarakonda, Siddhartha; Deshpande, Aditya; Damrauer, Jeffrey S; Silva, Tiago Chedraoui; Wong, Christopher K; Choi, Hyo Young; Felau, Ina; Robertson, A Gordon; Castro, Mauro A A; Bao, Lisui; Rheinbay, Esther; Liu, Eric Minwei; Trieu, Tuan; Haan, David; Yau, Christina; Hinoue, Toshinori; Liu, Yuexin; Shapira, Ofer; Kumar, Kiran; Mungall, Karen L; Zhang, Hailei; Lee, Jake June-Koo; Berger, Ashton; Gao, Galen F; Zhitomirsky, Binyamin; Liang, Wen-Wei; Zhou, Meng; Moorthi, Sitapriya; Berger, Alice H; Collisson, Eric A; Zody, Michael C; Ding, Li; Cherniack, Andrew D; Getz, Gad; Elemento, Olivier; Benz, Christopher C; Stuart, Josh; Zenklusen, J C; Beroukhim, Rameen; Chang, Jason C; Campbell, Joshua D; Hayes, D Neil; Yang, Lixing; Laird, Peter W; Weinstein, John N; Kwiatkowski, David J; Tsao, Ming S; Travis, William D.
Affiliation
  • Carrot-Zhang J; Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA.
  • Yao X; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA; New York Genome Center, New York, NY, USA; Tri-institutional Ph.D. Program in Computational Biology and Medicine, New York, NY, USA; Caryl and Israel Englander Institute for Precision Medicine and Meyer Cance
  • Devarakonda S; Section of Medical Oncology, Division of Oncology, Washington University School of Medicine, St. Louis, MO, USA; Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO, USA.
  • Deshpande A; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA; New York Genome Center, New York, NY, USA; Tri-institutional Ph.D. Program in Computational Biology and Medicine, New York, NY, USA; Caryl and Israel Englander Institute for Precision Medicine and Meyer Cance
  • Damrauer JS; Department of Genetics, Computational Medicine Program, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Silva TC; Center for Bioinformatics and Functional Genomics, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Wong CK; Department of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA, USA.
  • Choi HY; University of Tennessee Health Science Center, UTHSC Center for Cancer Research, TN, USA.
  • Felau I; National Cancer Institute, Bethesda, MD, USA.
  • Robertson AG; Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC, Canada.
  • Castro MAA; Bioinformatics and Systems Biology Laboratory, Federal University of Paraná, Curitiba, PR, Brazil.
  • Bao L; Ben May Department for Cancer Research, University of Chicago, Chicago, IL, USA.
  • Rheinbay E; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Massachusetts General Hospital Cancer Center, Boston, MA, USA.
  • Liu EM; Caryl and Israel Englander Institute for Precision Medicine and Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.
  • Trieu T; Caryl and Israel Englander Institute for Precision Medicine and Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.
  • Haan D; Department of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA, USA.
  • Yau C; University of California, San Francisco, San Francisco, CA, USA; Buck Institute for Research on Aging, Novato, CA, USA.
  • Hinoue T; Van Andel Institute, Grand Rapids, MI, USA.
  • Liu Y; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Shapira O; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Kumar K; Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Mungall KL; Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC, Canada.
  • Zhang H; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Lee JJ; Harvard Medical School, Boston, MA, USA.
  • Berger A; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Gao GF; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Zhitomirsky B; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Massachusetts General Hospital Cancer Center, Boston, MA, USA.
  • Liang WW; Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO, USA; McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO, USA.
  • Zhou M; Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA.
  • Moorthi S; Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Berger AH; Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Collisson EA; University of California, San Francisco, San Francisco, CA, USA.
  • Zody MC; New York Genome Center, New York, NY, USA.
  • Ding L; Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO, USA; McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO, USA.
  • Cherniack AD; Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Getz G; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Massachusetts General Hospital Cancer Center, Boston, MA, USA.
  • Elemento O; Tri-institutional Ph.D. Program in Computational Biology and Medicine, New York, NY, USA; Caryl and Israel Englander Institute for Precision Medicine and Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.
  • Benz CC; Buck Institute for Research on Aging, Novato, CA, USA.
  • Stuart J; Department of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA, USA.
  • Zenklusen JC; National Cancer Institute, Bethesda, MD, USA.
  • Beroukhim R; Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Chang JC; Thoracic Pathology, Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Campbell JD; Division of Computational Biomedicine, Boston University School of Medicine, Boston, MA, USA.
  • Hayes DN; University of Tennessee Health Science Center, UTHSC Center for Cancer Research, TN, USA.
  • Yang L; Ben May Department for Cancer Research, University of Chicago, Chicago, IL, USA.
  • Laird PW; Van Andel Institute, Grand Rapids, MI, USA.
  • Weinstein JN; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Kwiatkowski DJ; Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Tsao MS; Department of Pathology, University Health Network, Princess Margaret Cancer Centre, Toronto, ON, Canada.
  • Travis WD; Thoracic Pathology, Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Cell Rep ; 34(5): 108707, 2021 02 02.
Article in En | MEDLINE | ID: mdl-33535033
RTK/RAS/RAF pathway alterations (RPAs) are a hallmark of lung adenocarcinoma (LUAD). In this study, we use whole-genome sequencing (WGS) of 85 cases found to be RPA(-) by previous studies from The Cancer Genome Atlas (TCGA) to characterize the minority of LUADs lacking apparent alterations in this pathway. We show that WGS analysis uncovers RPA(+) in 28 (33%) of the 85 samples. Among the remaining 57 cases, we observe focal deletions targeting the promoter or transcription start site of STK11 (n = 7) or KEAP1 (n = 3), and promoter mutations associated with the increased expression of ILF2 (n = 6). We also identify complex structural variations associated with high-level copy number amplifications. Moreover, an enrichment of focal deletions is found in TP53 mutant cases. Our results indicate that RPA(-) cases demonstrate tumor suppressor deletions and genome instability, but lack unique or recurrent genetic lesions compensating for the lack of RPAs. Larger WGS studies of RPA(-) cases are required to understand this important LUAD subset.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Tachykinins / Kelch-Like ECH-Associated Protein 1 / Whole Genome Sequencing / Adenocarcinoma of Lung / Lung Neoplasms Limits: Humans Language: En Journal: Cell Rep Year: 2021 Document type: Article Affiliation country: Country of publication:
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Tachykinins / Kelch-Like ECH-Associated Protein 1 / Whole Genome Sequencing / Adenocarcinoma of Lung / Lung Neoplasms Limits: Humans Language: En Journal: Cell Rep Year: 2021 Document type: Article Affiliation country: Country of publication: