Frequent genomic rearrangements of BRCA1 associated protein-1 (BAP1) gene in Japanese malignant mesothelioma-characterization of deletions at exon level.
Frequent genomic rearrangements of BRCA1 associated protein-1 (BAP1) gene in Japanese malignant mesothelioma-characterization of deletions at exon level.
复制标题
日本恶性间皮瘤中 BRCA1 相关蛋白 1 (BAP1) 基因的频繁基因组重排——外显子水平缺失的表征。
DOI：
10.1038/jhg.2015.91
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发表时间：
2015
期刊：
影响因子：
3.5
通讯作者：
Emi M et al
中科院分区：
文献类型：
--
作者：
Hayashi Y;Iwasaki Y;Yoshikura N;Asano T;Hatano T;Tatsumi S;Satoh K;Kimura A;Kitamoto T;Yoshida M;Inuzuka T.;Emi M et al
恶性间皮瘤（MM）是一种与石棉有关的恶性肿瘤，起源于胸膜和腹膜腔的表面浆膜细胞。BRCA 1相关蛋白-1（BAP 1）基因的体细胞突变最近在白种人和日本人的MM以及葡萄膜黑色素瘤和肾癌中被发现。然而，突变的频率在报道的研究中有所不同，这可能是由于存在未检测到的BAP 1基因的总重排，这些重排可能会逃避测序策略的检测。我们通过多重连接依赖性探针扩增（MLPA）研究了17例日本MM肿瘤中BAP 1基因总基因组重排的存在和频率。我们发现5例肿瘤存在BAP 1基因部分缺失，每例肿瘤均存在外显子1-4（MM 39）、外显子1-5（MM 48）、外显子11-17（MM 57）、外显子1- 1 - 5（MM 19）和外显子1-16（MM 21）的部分缺失。两个肿瘤（MM 34，MM 14）有双等位基因缺失，四个肿瘤（MM 29，MM 35，MM 45和MM 56）有整个BAP 1基因的单等位基因缺失。因此，MLPA分析显示65%（11/17）的MM中存在BAP 1基因的大基因重排。异常高频率的大缺失表明BAP 1基因周围的3 p21染色体区域结构不稳定。MLPA可用于在外显子水平上精确地表征BAP 1基因的单等位基因和双等位基因缺失。
Malignant mesothelioma (MM) is an asbestos-related malignancy arising from surface serosal cells of pleural and peritoneal cavities. Somatic mutations of BRCA1 associated protein-1 (BAP1) gene were recently found in MM as well as in uveal melanoma and kidney cancer among the Caucasian and Japanese people. However, frequency of mutations varies among the reported studies, which might be due to presence of undetected gross rearrangements of BAP1 gene that might escape detection by sequencing strategy. We investigated the presence and frequency of gross genomic rearrangements in the BAP1 gene by multiplex ligation-dependent probe amplification (MLPA) in 17 Japanese cases of MM tumors. We found five tumors with partial deletion of BAP1 gene; each tumors displayed partial deletion of exons 1–4 (MM39), exons 1–5 (MM48), exons 11–17 (MM57), exons 1–15 (MM19) and exons 1–16 (MM21). Two tumors (MM34, MM14) had biallelic deletion and four tumors (MM29, MM35, MM45 and MM56) had monoallelic deletion of entire BAP1 gene. Therefore, MLPA analysis revealed large gene rearrangements of BAP1 gene in 65% of MM (11/17). Unusually high frequency of large deletions indicates that the 3p21 chromosomal region surrounding BAP1 gene is structurally unstable. MLPA was useful in characterizing both monoallelic and biallelic deletion of BAP1 gene precisely at exon level.