title: The potential utility of re-mining results of somatic mutation testing: KRAS status in lung adenocarcinoma.
abstract: KRAS mutant non-small cell lung cancers (NSCLCs) vary in clinical outcome depending on which specific KRAS mutation is present. Shorter progression free survival has been associated with KRAS variants G12C and G12V. Cell lines with these variants depend to a greater extent on the RAS/RAF/MEK/ERK signaling pathway and become more susceptible to MEK inhibition. Because different KRAS mutations may lead to altered drug sensitivity, we aimed to determine specific KRAS mutation status in a NSCLC patient cohort at our institution. A total of 502 NSCLC samples were screened for somatic mutations using the 50 gene AmpliSeq™ Cancer Hotspot Panel v2 (CHPv2). However only samples positive for variants in the KRAS gene were included in this study. Variants identified in the KRAS genes were curated using publicly available databases. The overall mutation rate in the KRAS gene was 32.7% (164/502). The most common KRAS mutations were G12C (41%), G12V (19%), and G12D (14%) along with less frequent variants. After re-mining our sequencing data, we found that more than a half of our KRAS mutant NSCLC patients could potentially benefit from the addition of a MEK inhibitor such as selumetinib to standard chemotherapeutic agents. Due to mutated KRAS, these patients will likely fail traditional anti-EGFR therapies but be eligible for newer combination therapies.
authors.affiliation: Department of Pathology and Laboratory Medicine, Dartmouth Hitchcock Medical Center and Norris Cotton Cancer Center, Lebanon, NH, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Biernacka
authors.affiliation: the Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Tsongalis
authors.affiliation: Department of Pathology and Laboratory Medicine, Dartmouth Hitchcock Medical Center and Norris Cotton Cancer Center, Lebanon, NH, USA.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Peterson
authors.affiliation: Department of Pathology and Laboratory Medicine, Dartmouth Hitchcock Medical Center and Norris Cotton Cancer Center, Lebanon, NH, USA.
authors.forename: Francine B
authors.initials: FB
authors.lastname: de Abreu
authors.affiliation: Department of Pathology and Laboratory Medicine, Dartmouth Hitchcock Medical Center and Norris Cotton Cancer Center, Lebanon, NH, USA.
authors.forename: Candice C
authors.initials: CC
authors.lastname: Black
authors.affiliation: Department of Pathology and Laboratory Medicine, Dartmouth Hitchcock Medical Center and Norris Cotton Cancer Center, Lebanon, NH, USA.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Gutmann
authors.affiliation: Department of Pathology and Laboratory Medicine, Dartmouth Hitchcock Medical Center and Norris Cotton Cancer Center, Lebanon, NH, USA.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pathology and Laboratory Medicine, Dartmouth Hitchcock Medical Center and Norris Cotton Cancer Center, Lebanon, NH, USA.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Tafe
authors.affiliation: the Geisel School of Medicine at Dartmouth, Hanover, NH, USA; Department of Community and Family Medicine, Dartmouth Hitchcock Medical Center and Norris Cotton Cancer Center, Lebanon, NH, USA.
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Amos
authors.affiliation: Department of Pathology and Laboratory Medicine, Dartmouth Hitchcock Medical Center and Norris Cotton Cancer Center, Lebanon, NH, USA; the Geisel School of Medicine at Dartmouth, Hanover, NH, USA. Electronic address: Gregory.j.tsongalis@hitchcock.org.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Tsongalis
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001562:Benzimidazoles / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D057225:Data Mining; D018572:Disease-Free Survival; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D057285:Precision Medicine; D016283:Proto-Oncogene Proteins p21(ras) / Q000737:chemistry / Q000235:genetics*; D043823:Taxoids / Q000627:therapeutic use
chemical_list: C517975:AZD 6244; D000970:Antineoplastic Agents; D001562:Benzimidazoles; C117307:KRAS protein, human; D043823:Taxoids; D000077143:Docetaxel; D016283:Proto-Oncogene Proteins p21(ras)
keywords: KRAS; Somatic mutation; data mining; lung cancer; next generation sequencing