Tumor-specific exon creation of the HELLS/SMARCA6 gene in non-small cell lung cancer
Tumor-specific exon creation of the HELLS/SMARCA6 gene in non-small cell lung cancer
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DOI：
10.1002/ijc.20407
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发表时间：
2004-10-20
影响因子：
6.4
通讯作者：
Shimizu, K
中科院分区：
文献类型：
--
作者：
Yano, M;Ouchida, M;Shimizu, K
为了鉴定非小细胞肺癌中10号染色体上的肿瘤抑制基因，我们分离了10种类型的HELLS/SMARCA 6基因转录本的剪接变体。HELLS/SMARCA 6是SNF 2家族的新成员，与染色质重塑等细胞功能密切相关。变体I是在外显子3和4之间插入44 nt内含子序列的选择性剪接同种型，导致翻译提前终止。变体I的表达仅在肺癌标本中检测到（43例，26%），但在相应的正常组织中未检测到。与侧翼标记（25-31%）相比，在HELLS/SMARCA 6基因附近的D10 S520标记显示普遍的等位基因丢失（41%）。这些结果表明，由等位基因丢失引起的HELLS/SMARCA 6功能丧失和由肿瘤特异性外显子产生的异常蛋白可能导致表观遗传失调，导致肺细胞恶性化或其进展。(C)2004 Wiley-Liss，Inc.
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 I 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 I was detected exclusively in lung cancer specimens (I I 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. (C) 2004 Wiley-Liss, Inc.