Tumor‐specific exon creation of the HELLS/SMARCA6 gene in non‐small cell lung cancer

• Published in: International journal of cancer Vol. 112; no. 1; pp. 8 - 13
• Main Authors: Yano, Masaaki, Ouchida, Mamoru, Shigematsu, Hisayuki, Tanaka, Noriyoshi, Ichimura, Koichi, Kobayashi, Kazuyasu, Inaki, Yasuhiko, Toyooka, Shinichi, Tsukuda, Kazunori, Shimizu, Nobuyoshi, Shimizu, Kenji
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 20.10.2004; Wiley-Liss
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Aged; Alternative Splicing; Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Case-Control Studies; Chromosomes, Human, Pair 10 - genetics; Disease Progression; DNA - genetics; DNA Helicases - genetics; DNA Helicases - metabolism; Exons - genetics; Female; HELLS; Humans; Immunoenzyme Techniques; Loss of Heterozygosity; lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Male; Medical sciences; Pneumology; Reverse Transcriptase Polymerase Chain Reaction; SMARCA6; Tumors; Tumors of the respiratory system and mediastinum; Chromosomal aberration; Human; Lung disease; Alternative splicing; Respiratory disease; Genetic variant; Lung cancer; Malignant tumor; non-small cell lung carcinoma; Gene expression; Carcinogenesis; Cancerology; Exon; Loss of heterozygosity; Cytogenetics; Deletion; Bronchus disease; Abnormal chromosome; Genetics; Abnormal chromosome C10; Tumor suppressor gene
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.20407

To identify tumor‐suppressor genes on chromosome 10 in non‐small cell lung cancers, we isolated 10 types of splicing variant of the HELLS/SMARCA6 gene transcripts. HELLS/SMARCA6 is a novel member of SNF2 family, which is implicated in cellular functions like chromatin remodeling. Variant 1 was an alternatively spliced isoform containing an insertion of a 44 ntd intronic sequence between exons 3 and 4, giving rise to a premature termination of translation. Expression of variant 1 was detected exclusively in lung cancer specimens (11 of 43 cases, 26%) but was not detected in corresponding normal tissues. The D10S520 marker in the proximity of the HELLS/SMARCA6 gene showed prevalent allelic loss (41%) compared to flanking markers (25–31%). These results suggest that loss of function of HELLS/SMARCA6 by allelic loss and aberrant proteins by tumor‐specific exon creation may result in epigenetic deregulation, leading lung cells to malignancy or its progression. © 2004 Wiley‐Liss, Inc.