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人类结直肠癌中分泌型磷脂酶A2基因改变的缺失

Absence of secretory phospholipase A2 gene alterations in human colorectal cancer.

作者信息

Riggins G J, Markowitz S, Wilson J K, Vogelstein B, Kinzler K W

机构信息

Johns Hopkins Oncology Center, Baltimore, Maryland 21231, USA.

出版信息

Cancer Res. 1995 Nov 15;55(22):5184-6.

PMID:7585570
Abstract

A potent modifying locus of intestinal tumorigenesis in the mouse was recently identified as secretory phospholipase A2 (sPLA2). The human homologue of sPLA2 maps to chromosome 1p35, a region frequently lost in human tumors. To evaluate the possibility that sPLA2 was a tumor suppressor gene that was the target of the 1p loss events, we identified polymorphisms within the human sPLA2 gene. Using these polymorphisms, 31% of 16 colorectal carcinomas were found to lose a sPLA2 allele. However, sequence analysis of the complete coding region of sPLA2 revealed no somatic mutations in the remaining allele of those tumors with allelic loss, nor in 18 additional colorectal cancers. Thus, sPLA2 is within the chromosomal region often lost during colorectal tumorigenesis, but mutations of this gene do not appear to play a major role in colorectal cancer development, and sPLA2 is unlikely to be the 1p35 tumor suppressor.

摘要

最近,小鼠肠道肿瘤发生的一个强效修饰位点被确定为分泌型磷脂酶A2(sPLA2)。sPLA2的人类同源基因定位于1p35染色体,该区域在人类肿瘤中经常缺失。为了评估sPLA2是肿瘤抑制基因且是1p缺失事件靶点的可能性,我们鉴定了人类sPLA2基因内的多态性。利用这些多态性,在16例结直肠癌中有31%被发现缺失一个sPLA2等位基因。然而,对sPLA2完整编码区的序列分析显示,在那些等位基因缺失的肿瘤的剩余等位基因中,以及在另外18例结直肠癌中,均未发现体细胞突变。因此,sPLA2位于结直肠癌发生过程中经常缺失的染色体区域,但该基因的突变似乎在结直肠癌发展中不起主要作用,并且sPLA2不太可能是1p35肿瘤抑制基因。

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