title: Mutational analysis of the HER2 gene in lung tumors from Caucasian patients: mutations are mainly present in adenocarcinomas with bronchioloalveolar features.
abstract: Activating mutations in the tyrosine kinase domain of the HER2 gene have recently been reported in lung adenocarcinomas, mainly in East Asian patients. Our study was devised to evaluate the prevalence and nature of HER2 mutations in lung adenocarcinomas from Caucasian patients. The mutational status of the HER2 gene was evaluated in 403 lung adenocarcinomas by PCR-single strand conformation polymorphism analysis and direct sequencing of Exons 19 and 20. We found HER2 mutations in 9 (2.2%) cases. Seven (78%) of the mutations were in frame duplications/insertions at codons 776-779 (YVMA), the other 2 were base substitutions resulting in aminoacid changes. The hotspot mutation at bases 776-779 was previously found to be the most frequent HER2 mutation in Asiatic patients. The distribution of mutations was significantly different between conventional lung adenocarcinomas (CLAs) and lung adenocarcinomas with bronchioloalveolar features (ABAFs). Seven (6.2%) of 113 ABAFs and 2 (0.7%) of 290 CLA were mutated (p = 0.0025). In addition, the frequency of HER2 mutations was slightly higher in females (4.1%) than in males (1.8%) and in never smokers (3.1%) than in smokers (1.9%), but differences were not statistically significant. This series of tumors was also investigated for EGFR and K-ras mutations. EGFR mutations were observed in 43 (10.7%) cases, and K-ras mutations in 110 (27.3%) cases. EGFR, HER2 and K-ras mutations were found to be mutually exclusive events. The presence of HER2 mutations in a subset of patients with lung adenocarcinoma raise hope to treat these patients with HER2 specific kinase inhibitors.
authors.affiliation: Clinical Research Center, Center of Excellence on Aging, University-Foundation, Chieti, Italy.
authors.forename: Fiamma
authors.initials: F
authors.lastname: Buttitta
authors.forename: Fabio
authors.initials: F
authors.lastname: Barassi
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Fresu
authors.forename: Lara
authors.initials: L
authors.lastname: Felicioni
authors.forename: Antonio
authors.initials: A
authors.lastname: Chella
authors.forename: Diego
authors.initials: D
authors.lastname: Paolizzi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lattanzio
authors.forename: Simona
authors.initials: S
authors.lastname: Salvatore
authors.forename: Pier P
authors.initials: PP
authors.lastname: Camplese
authors.forename: Sandra
authors.initials: S
authors.lastname: Rosini
authors.forename: Teodorico
authors.initials: T
authors.lastname: Iarussi
authors.forename: Felice
authors.initials: F
authors.lastname: Mucilli
authors.forename: Rocco
authors.initials: R
authors.lastname: Sacco
authors.forename: Andrea
authors.initials: A
authors.lastname: Mezzetti
authors.forename: Antonio
authors.initials: A
authors.lastname: Marchetti
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D017931:DNA Primers; D066246:ErbB Receptors / Q000235:genetics; D018734:Genes, erbB-2; D011905:Genes, ras; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D044465:White People
chemical_list: D017931:DNA Primers; D066246:ErbB Receptors