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High throughput mutation profiling of lung adenocarcinoma
Author(s) -
Sholl Lynette Marie,
Garcia Elizabeth,
Jia Yonghui,
MacConaill Laura,
Lindeman Neal
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.58.4
Subject(s) - kras , cdkn2a , stk11 , cancer research , adenocarcinoma , genotyping , gnas complex locus , cold pcr , biology , mutation , medicine , gene , microbiology and biotechnology , genetics , point mutation , cancer , genotype
Mutation profiling of lung adenocarcinoma (ACA) identifies patients for targeted therapies and clinical trials. We utilize a high throughput genotyping platform to examine mutations in common oncogenes and tumor suppressor genes (TSG) in lung ACA. Fresh frozen or formalin‐fixed paraffin‐embedded tumors were collected following written informed consent. DNA was extracted from specimens containing >;50% tumor cells using standard methods. Mutation profiling for 471 mutations in 41 genes was performed using single base extension chemistry followed by MALDI‐TOF mass spectrophotometry (Sequenom). Variant alleles were confirmed with homogenous MassEXTEND chemistry. 173 lung ACA were tested. 96 (55%) tumors contained ≥1 mutation. KRAS was most commonly mutated (57 tumors; 33%), followed by EGFR (17 tumors; 10%), BRAF (10 tumors; 6%) and CTNNB1 (7 tumors; 4%). Five cases had concurrent CTNNB1 and EGFR or KRAS mutations. PIK3CA, PTEN, STK11, TP53, CDKN2A, VHL, ERBB2, GNAS, MAP2K1 and IDH1 mutations were detected in <2% of tumors. Over half of unselected lung ACA samples had at least one mutation in this panel. This genotyping strategy underestimates the frequency of TSG mutations, where alterations are dispersed throughout the coding sequence, and has low sensitivity for variable insertion/deletion mutations, limitations that can be addressed by adoption of next generation sequencing.