title: Somatic STK11 and concomitant STK11/KRAS mutational frequency in stage IV lung adenocarcinoma adrenal metastases.
abstract: Somatic serine/threonine kinase 11 (STK11) also known as liver kinase B1 (LKB1) is a tumor suppressor gene and ranks as the third most frequently mutated gene in lung adenocarcinoma. However, current molecular testing guidelines recommend evaluating for epidermal growth factor receptor mutations and ALK fusions to guide therapy in all patients with advanced stage adenocarcinoma, regardless of gender, race, or smoking history. Identifying alternative "driver" mutations and using actionable targeted pharmacotherapy is a key approach to providing effective individualized medical care. The analytical sensitivity and parallel multigene approach of targeted next-generation sequencing is an attractive methodology for use for cytology specimens. The presented lung adenocarcinoma study revealed that STK11 mutations alone and concomitant KRAS/STK11 mutations were identified in 18.2% and 4.5% of solitary adrenal metastases, respectively. Molecular profiling of epidermal growth factor receptor tyrosine kinase inhibitor resistant tumors may help to identify patients who would most benefit from alternative single or dual pathway inhibition potentially leading to a revision in current molecular testing guidelines.
authors.affiliation: *Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota; †Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota; ‡Division of Biomedical Statics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota; and §Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Ferga C
authors.initials: FC
authors.lastname: Gleeson
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Kipp
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Levy
authors.forename: Jesse S
authors.initials: JS
authors.lastname: Voss
authors.forename: Michael B
authors.initials: MB
authors.lastname: Campion
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Minot
authors.forename: Zheng J
authors.initials: ZJ
authors.lastname: Tu
authors.forename: Eric W
authors.initials: EW
authors.lastname: Klee
authors.forename: Konstantinos N
authors.initials: KN
authors.lastname: Lazaridis
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Kerr
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000310:Adrenal Gland Neoplasms / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005500:Follow-Up Studies; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D015996:Survival Rate
chemical_list: C117307:KRAS protein, human; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases; D016283:Proto-Oncogene Proteins p21(ras)