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.
Yano
Masaaki
M
Department of Surgical Oncology and Thoracic Surgery, Graduate School of Medicine and Dentistry, Okayama University, Okayama, Japan.
Ouchida
Mamoru
M
Shigematsu
Hisayuki
H
Tanaka
Noriyoshi
N
Ichimura
Koichi
K
Kobayashi
Kazuyasu
K
Inaki
Yasuhiko
Y
Toyooka
Shinichi
S
Tsukuda
Kazunori
K
Shimizu
Nobuyoshi
N
Shimizu
Kenji
K
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