The Frequency of Ras Mutations in Cancer

被引:707
作者
Prior, Ian A. [1 ]
Hood, Fiona E. [1 ]
Hartley, James L. [2 ]
机构
[1] Univ Liverpool, Inst Translat Med, Div Cellular & Mol Physiol, Liverpool, Merseyside, England
[2] NCI RAS Initiat, Canc Res Technol Program, Frederick Natl Lab Canc Res, Frederick, MD USA
基金
美国国家卫生研究院;
关键词
H-RAS; K-RAS; N-RAS; BIOCHEMICAL-PROPERTIES; BIOLOGICAL-PROPERTIES; TISSUE-SPECIFICITY; KRAS; PATTERNS; DRIVEN; INHIBITORS;
D O I
10.1158/0008-5472.CAN-19-3682
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Ras is frequently mutated in cancer, however, there is a lack of consensus in the literature regarding the cancer mutation frequency of Ras, with quoted values varying from 10%-30%. This variability is at least in part due to the selective aggregation of data from different databases and the dominant influence of particular cancer types and particular Ras isoforms within these datasets. To provide a more definitive figure for Ras mutation frequency in cancer, we cross-referenced the data in all major publicly accessible cancer mutation databases to determine reliable mutation frequency values for each Ras isoform in all major cancer types. These percentages were then applied to current U.S. cancer incidence statistics to estimate the number of new patients each year that have Ras-mutant cancers. We find that approximately 19% of patients with cancer harbor Ras mutations, equivalent to approximately 3.4 million new cases per year worldwide. We discuss the Ras isoform and mutation-specific trends evident within the datasets that are relevant to current Ras-targeted therapies.
引用
收藏
页码:2969 / 2974
页数:6
相关论文
共 55 条
[41]   Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16(INK4a) [J].
Serrano, M ;
Lin, AW ;
McCurrach, ME ;
Beach, D ;
Lowe, SW .
CELL, 1997, 88 (05) :593-602
[42]   RAS Proteins and Their Regulators in Human Disease [J].
Simanshu, Dhirendra K. ;
Nissley, Dwight V. ;
McCormick, Frank .
CELL, 2017, 170 (01) :17-33
[43]   Real-Time Targeted Genome Profile Analysis of Pancreatic Ductal Adenocarcinomas Identifies Genetic Alterations That Might Be Targeted With Existing Drugs or Used as Biomarkers [J].
Singhi, Aatur D. ;
George, Ben ;
Greenbowe, Joel R. ;
Chung, Jon ;
Suh, James ;
Maitra, Anirban ;
Klempner, Samuel J. ;
Hendifar, Andrew ;
Milind, Javle M. ;
Golan, Talia ;
Brand, Randall E. ;
Zureikat, Amer H. ;
Roy, Somak ;
Schrock, Alexa B. ;
Miller, Vincent A. ;
Ross, Jeffrey S. ;
Ali, Siraj M. ;
Bahary, Nathan .
GASTROENTEROLOGY, 2019, 156 (08) :2242-+
[44]   NMR-based functional profiling of RASopathies and oncogenic RAS mutations [J].
Smith, Matthew J. ;
Neel, Benjamin G. ;
Ikura, Mitsuhiko .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (12) :4574-4579
[45]   Comparative analysis of KRAS codon 12, 13, 18, 61, and 117 mutations using human MCF10A isogenic cell lines [J].
Stolze, Britta ;
Reinhart, Stefanie ;
Bulllinger, Lars ;
Froehling, Stefan ;
Scholl, Claudia .
SCIENTIFIC REPORTS, 2015, 5
[46]   Comprehensive Genomic Profiling Facilitates Implementation of the National Comprehensive Cancer Network Guidelines for Lung Cancer Biomarker Testing and Identifies Patients Who May Benefit From Enrollment in Mechanism-Driven Clinical Trials [J].
Suh, James H. ;
Johnson, Adrienne ;
Albacker, Lee ;
Wang, Kai ;
Chmielecki, Juliann ;
Frampton, Garrett ;
Gay, Laurie ;
Elvin, Julia A. ;
Vergilio, Jo-Anne ;
Ali, Siraj ;
Miller, Vincent A. ;
Stephens, Philip J. ;
Ross, Jeffrey S. .
ONCOLOGIST, 2016, 21 (06) :684-691
[47]   COSMIC: the Catalogue Of Somatic Mutations In Cancer [J].
Tate, John G. ;
Bamford, Sally ;
Jubb, Harry C. ;
Sondka, Zbyslaw ;
Beare, David M. ;
Bindal, Nidhi ;
Boutselakis, Harry ;
Cole, Charlotte G. ;
Creatore, Celestino ;
Dawson, Elisabeth ;
Fish, Peter ;
Harsha, Bhavana ;
Hathaway, Charlie ;
Jupe, Steve C. ;
Kok, Chai Yin ;
Noble, Kate ;
Ponting, Laura ;
Ramshaw, Christopher C. ;
Rye, Claire E. ;
Speedy, Helen E. ;
Stefancsik, Ray ;
Thompson, Sam L. ;
Wang, Shicai ;
Ward, Sari ;
Campbell, Peter J. ;
Forbes, Simon A. .
NUCLEIC ACIDS RESEARCH, 2019, 47 (D1) :D941-D947
[48]   Distinct Binding Preferences between Ras and Raf Family Members and the Impact on Oncogenic Ras Signaling [J].
Terrell, Elizabeth M. ;
Durrant, David E. ;
Ritt, Daniel A. ;
Sealover, Nancy E. ;
Sheffels, Erin ;
Spencer-Smith, Russell ;
Esposito, Dominic ;
Zhou, Yong ;
Hancock, John F. ;
Kortum, Robert L. ;
Morrison, Deborah K. .
MOLECULAR CELL, 2019, 76 (06) :872-+
[49]   BIOCHEMICAL AND BIOLOGICAL PROPERTIES OF THE HUMAN N-RAS P21 PROTEIN [J].
TRAHEY, M ;
MILLEY, RJ ;
COLE, GE ;
INNIS, M ;
PATERSON, H ;
MARSHALL, CJ ;
HALL, A ;
MCCORMICK, F .
MOLECULAR AND CELLULAR BIOLOGY, 1987, 7 (01) :541-544
[50]   K- and N-Ras are geranylgeranylated in cells treated with farnesyl protein transferase inhibitors [J].
Whyte, DB ;
Kirschmeier, P ;
Hockenberry, TN ;
NunezOliva, I ;
James, L ;
Catino, JJ ;
Bishop, WR ;
Pai, JK .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (22) :14459-14464