Tumor-specific exon creation of the HELLS/SMARCA6 gene in non-small cell lung cancer.
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.
Department of Surgical Oncology and Thoracic Surgery, Graduate School of Medicine and Dentistry, Okayama University, Okayama, Japan.
Masaaki
M
Yano
Mamoru
M
Ouchida
Hisayuki
H
Shigematsu
Noriyoshi
N
Tanaka
Koichi
K
Ichimura
Kazuyasu
K
Kobayashi
Yasuhiko
Y
Inaki
Shinichi
S
Toyooka
Kazunori
K
Tsukuda
Nobuyoshi
N
Shimizu
Kenji
K
Shimizu
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000368:Aged; D017398:Alternative Splicing; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D004247:DNA / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D005091:Exons / Q000235:genetics*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004247:DNA; D004265:DNA Helicases; C412063:HELLS protein, human