title: Somatic mutations of the HER2 in metastatic breast cancer.
abstract: Mutations in the epidermal growth factor receptor gene (EGFR) in lung cancers predict for sensitivity to EGFR kinase inhibitors. HER2 (also known as NEU, EGFR2, or ERBB2) is a member of the EGFR family of receptor tyrosine kinases and plays important roles in the pathogenesis of certain human cancers, and mutations have recently been reported in lung cancers. We sequenced the full length of HER2 in 198 metastatic breast cancers (MBC) as well as 34 other epithelial cancers (bladder, prostate, and colorectal cancers) and compared the mutational status with clinic pathologic features and the presence of EGFR or KRAS mutations. HER2 mutations were present in 11.6 % (23 of 198) of MBC and were absent in other types of cancers. HER2 mutations were located in exon 15 and the in-frame insertions in exon 20 with corresponding region as did EGFR insertions. HER2 mutations were significantly more frequent in patient after the administration of trastuzumab (34.8 %, 8 of 23; P = 0.02). Mutations in exon 15 and 20 were more potent than wild-type HER2 in associating with activating signal transducers and inducing survival, invasiveness, and tumorigenicity.
authors.affiliation: Department of Breast Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Fang
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Jiang
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Xue
authors.initials: X
authors.lastname: Yang
authors.forename: Yinqi
authors.initials: Y
authors.lastname: Gao
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics; D005091:Exons; D005260:Female; D006801:Humans; D009154:Mutation; D009362:Neoplasm Metastasis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D000068878:Trastuzumab; D018631:ras Proteins / Q000235:genetics
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; D018631:ras Proteins; C117307:KRAS protein, human