Premium
Contribution of germline mutations to PARK2 gene inactivation in lung adenocarcinoma
Author(s) -
Iwakawa Reika,
Okayama Hirokazu,
Kohno Takashi,
SatoOtsubo Aiko,
Ogawa Seishi,
Yokota Jun
Publication year - 2012
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.21933
Subject(s) - loss of heterozygosity , germline , biology , genetics , germline mutation , point mutation , mutation , gene , gene duplication , cancer research , allele
Homozygous germline mutations of the PARK2 gene are responsible for the development of early‐onset Parkinson's disease (PD). Homozygous PARK2 mutations have been also detected in lung adenocarcinoma (LADC). However, since heterozygous PARK2 germline mutations are present in a subset of non‐PD individuals, the timing for the occurrence of two‐hit PARK2 mutations in LADC progression is unclear. Therefore, we comprehensively analyzed mutations, expression and copy number variations of the PARK2 gene in 267 primary LADCs together with the corresponding noncancerous lung cells and 39 LADC cell lines. Heterozygous germline exonic deletions were detected in five patients with LADC, and loss of heterozygosity including the PARK2 locus was detected in 31/267 (11.6%) LADCs. However, homozygous PARK2 inactivation was not detected in any of them, including the five patients with germline mutations. Homozygous PARK2 inactivation was detected in 6/39 (15%) cell lines, two exonic deletions, one exonic duplication, and three point mutations, while heterozygous PARK2 inactivation was detected in two cell lines (both by exonic deletions). These results strongly indicate that somatic PARK2 mutations occur rarely (or do not occur) in LADC development and that germline PARK2 mutations could contribute to LADC progression but not to LADC development. © 2012 Wiley Periodicals, Inc.