TY - JOUR
T1 - LKB1 mutations frequently detected in mucinous bronchioloalveolar carcinoma
AU - Osoegawa, Atsushi
AU - Kometani, Takuro
AU - Nosaki, Kaname
AU - Ondo, Kaoru
AU - Hamatake, Motoharu
AU - Hirai, Fumihiko
AU - Seto, Takashi
AU - Sugio, Kenji
AU - Ichinose, Yukito
N1 - Funding Information:
This work was supported in part by a Grant-in-Aid for Cancer Research (16-1) from the Ministry of Health, Labour and Welfare of Japan and by a Grant-in-Aid for Young Scientists (B) No. 19790973 from the Japan Society for the Promotion of Science.
PY - 2011/9
Y1 - 2011/9
N2 - Objective: LKB1 mutations are common in patients with Peutz-Jeghers syndrome, which is characterized by mucocutaneous pigmentation, intestinal polyps and a high incidence of cancers at variable sites. This study investigated the status of the LKB1 gene in mucinous bronchioloalveolar carcinoma with or without Peutz-Jeghers syndrome. Methods: Three mucinous bronchioloalveolar carcinoma tumors from two Peutz-Jeghers syndrome patients and seven tumors from sporadic mucinous bronchioloalveolar carcinoma patients were collected by surgery between 2002 and 2008, and high molecular weight genomic DNA was extracted from them. The nucleotide sequences in exons 1-9 of LKB1 were determined by genomic polymerase chain reaction-direct sequencing. The loss of heterozygosity was analyzed by high-resolution fluorescent microsatellite analysis using two microsatellite markers that encompass the LKB1 locus, D19S886 and D19S565. The mutations of KRAS, EGFR and p53 were also evaluated. Results: The germline mutation of LKB1 in the Peutz-Jeghers syndrome patients was identified as G215D by analyzing genomic DNA from normal lung tissue specimens. Furthermore, two of the three mucinous bronchioloalveolar carcinomas from these Peutz-Jeghers syndrome patients exhibited additional somatic mutations. On the other hand, four of seven sporadic 'non-Peutz-Jeghers syndrome' mucinous bronchioloalveolar carcinomas had LKB1 mutations. Loss of heterozygosity analyses revealed allelic loss in two tumors with LKB1 mutations. As a result, 70% of the mucinous bronchioloalveolar carcinomas exhibited LKB1 mutations. KRAS, EGFR and p53 mutations were mutually exclusive and observed in four, two and one tumors, respectively. Among them, five mutations occurred concomitantly with LKB1 mutations. Conclusions: The relatively high frequency of LKB1 mutations in mucinous bronchioloalveolar carcinoma patients may therefore suggest its involvement in lung carcinogenesis, at least in mucinous bronchioloalveolar carcinoma.
AB - Objective: LKB1 mutations are common in patients with Peutz-Jeghers syndrome, which is characterized by mucocutaneous pigmentation, intestinal polyps and a high incidence of cancers at variable sites. This study investigated the status of the LKB1 gene in mucinous bronchioloalveolar carcinoma with or without Peutz-Jeghers syndrome. Methods: Three mucinous bronchioloalveolar carcinoma tumors from two Peutz-Jeghers syndrome patients and seven tumors from sporadic mucinous bronchioloalveolar carcinoma patients were collected by surgery between 2002 and 2008, and high molecular weight genomic DNA was extracted from them. The nucleotide sequences in exons 1-9 of LKB1 were determined by genomic polymerase chain reaction-direct sequencing. The loss of heterozygosity was analyzed by high-resolution fluorescent microsatellite analysis using two microsatellite markers that encompass the LKB1 locus, D19S886 and D19S565. The mutations of KRAS, EGFR and p53 were also evaluated. Results: The germline mutation of LKB1 in the Peutz-Jeghers syndrome patients was identified as G215D by analyzing genomic DNA from normal lung tissue specimens. Furthermore, two of the three mucinous bronchioloalveolar carcinomas from these Peutz-Jeghers syndrome patients exhibited additional somatic mutations. On the other hand, four of seven sporadic 'non-Peutz-Jeghers syndrome' mucinous bronchioloalveolar carcinomas had LKB1 mutations. Loss of heterozygosity analyses revealed allelic loss in two tumors with LKB1 mutations. As a result, 70% of the mucinous bronchioloalveolar carcinomas exhibited LKB1 mutations. KRAS, EGFR and p53 mutations were mutually exclusive and observed in four, two and one tumors, respectively. Among them, five mutations occurred concomitantly with LKB1 mutations. Conclusions: The relatively high frequency of LKB1 mutations in mucinous bronchioloalveolar carcinoma patients may therefore suggest its involvement in lung carcinogenesis, at least in mucinous bronchioloalveolar carcinoma.
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U2 - 10.1093/jjco/hyr102
DO - 10.1093/jjco/hyr102
M3 - Article
C2 - 21816872
AN - SCOPUS:80052497535
SN - 0368-2811
VL - 41
SP - 1132
EP - 1137
JO - Japanese journal of clinical oncology
JF - Japanese journal of clinical oncology
IS - 9
M1 - hyr102
ER -
