BACKGROUND: Several targeted therapies have been approved for treatment of solid tumors. Identification of gene mutations that indicate response to these therapies is rapidly progressing. A 34-gene next-generation sequencing (NGS) panel, developed and validated by us, was evaluated to detect additional mutations in community-based cancer specimens initially sent to our reference laboratory for routine molecular testing. METHODS: Consecutive de-identified clinical specimens (n = 121) from melanoma cases (n = 31), lung cancer cases (n = 27), colorectal cancer cases (n = 33), and breast cancer cases (n = 30) were profiled by NGS, and the results were compared with routine molecular testing. RESULTS: Upon initial mutation testing, 20 % (24/121) were positive. NGS detected ≥1 additional mutation not identified by routine testing in 74 % of specimens (90/121). Of the specimens with additional mutations, 16 harbored mutations in National Comprehensive Cancer Network guideline genes. These various additional mutations were in gene regions not routinely covered, in genes not routinely tested, and/or present at low allele frequencies. Moreover, NGS yielded no false negatives. Overall, NGS detected mutations in 59 % of the genes (20/34) included in the panel, 75 % of which (15/20) were detected in multiple tumor types. Mutations in TP53 were found in 51 % of tumors tested (62/121). Mutations in at least one other (non-TP53) gene present in the panel were detected in 64 % of cases (77/121). CONCLUSION: This assay provides improved breadth and sensitivity for profiling clinically relevant genes in these prevalent solid tumor types.
BACKGROUND: Several targeted therapies have been approved for treatment of solid tumors. Identification of gene mutations that indicate response to these therapies is rapidly progressing. A 34-gene next-generation sequencing (NGS) panel, developed and validated by us, was evaluated to detect additional mutations in community-based cancer specimens initially sent to our reference laboratory for routine molecular testing. METHODS: Consecutive de-identified clinical specimens (n = 121) from melanoma cases (n = 31), lung cancer cases (n = 27), colorectal cancer cases (n = 33), and breast cancer cases (n = 30) were profiled by NGS, and the results were compared with routine molecular testing. RESULTS: Upon initial mutation testing, 20 % (24/121) were positive. NGS detected ≥1 additional mutation not identified by routine testing in 74 % of specimens (90/121). Of the specimens with additional mutations, 16 harbored mutations in National Comprehensive Cancer Network guideline genes. These various additional mutations were in gene regions not routinely covered, in genes not routinely tested, and/or present at low allele frequencies. Moreover, NGS yielded no false negatives. Overall, NGS detected mutations in 59 % of the genes (20/34) included in the panel, 75 % of which (15/20) were detected in multiple tumor types. Mutations in TP53 were found in 51 % of tumors tested (62/121). Mutations in at least one other (non-TP53) gene present in the panel were detected in 64 % of cases (77/121). CONCLUSION: This assay provides improved breadth and sensitivity for profiling clinically relevant genes in these prevalent solid tumor types.
Authors: Richard D Carvajal; Cristina R Antonescu; Jedd D Wolchok; Paul B Chapman; Ruth-Ann Roman; Jerrold Teitcher; Katherine S Panageas; Klaus J Busam; Bartosz Chmielowski; Jose Lutzky; Anna C Pavlick; Anne Fusco; Lauren Cane; Naoko Takebe; Swapna Vemula; Nancy Bouvier; Boris C Bastian; Gary K Schwartz Journal: JAMA Date: 2011-06-08 Impact factor: 56.272
Authors: Jamie E Chaft; Maria E Arcila; Paul K Paik; Christopher Lau; Gregory J Riely; M Catherine Pietanza; Maureen F Zakowski; Valerie Rusch; Camelia S Sima; Marc Ladanyi; Mark G Kris Journal: Mol Cancer Ther Date: 2011-12-01 Impact factor: 6.261
Authors: Erin D Pleasance; R Keira Cheetham; Philip J Stephens; David J McBride; Sean J Humphray; Chris D Greenman; Ignacio Varela; Meng-Lay Lin; Gonzalo R Ordóñez; Graham R Bignell; Kai Ye; Julie Alipaz; Markus J Bauer; David Beare; Adam Butler; Richard J Carter; Lina Chen; Anthony J Cox; Sarah Edkins; Paula I Kokko-Gonzales; Niall A Gormley; Russell J Grocock; Christian D Haudenschild; Matthew M Hims; Terena James; Mingming Jia; Zoya Kingsbury; Catherine Leroy; John Marshall; Andrew Menzies; Laura J Mudie; Zemin Ning; Tom Royce; Ole B Schulz-Trieglaff; Anastassia Spiridou; Lucy A Stebbings; Lukasz Szajkowski; Jon Teague; David Williamson; Lynda Chin; Mark T Ross; Peter J Campbell; David R Bentley; P Andrew Futreal; Michael R Stratton Journal: Nature Date: 2009-12-16 Impact factor: 49.962
Authors: Nikhil Wagle; Eliezer M Van Allen; Daniel J Treacy; Dennie T Frederick; Zachary A Cooper; Amaro Taylor-Weiner; Mara Rosenberg; Eva M Goetz; Ryan J Sullivan; Deborah N Farlow; Dennis C Friedrich; Kristin Anderka; Danielle Perrin; Cory M Johannessen; Aaron McKenna; Kristian Cibulskis; Gregory Kryukov; Eran Hodis; Donald P Lawrence; Sheila Fisher; Gad Getz; Stacey B Gabriel; Scott L Carter; Keith T Flaherty; Jennifer A Wargo; Levi A Garraway Journal: Cancer Discov Date: 2013-11-21 Impact factor: 39.397
Authors: Simon A Forbes; David Beare; Prasad Gunasekaran; Kenric Leung; Nidhi Bindal; Harry Boutselakis; Minjie Ding; Sally Bamford; Charlotte Cole; Sari Ward; Chai Yin Kok; Mingming Jia; Tisham De; Jon W Teague; Michael R Stratton; Ultan McDermott; Peter J Campbell Journal: Nucleic Acids Res Date: 2014-10-29 Impact factor: 16.971