肾癌遗传学研究进展

Advances in genetics of kidney cancer

肾癌是一类具有多种组织类型及不同遗传背景的癌症。目前至少有10种类型的肾细胞癌。其中最常见的是透明肾细胞癌,其次是乳头状肾细胞癌、嫌色肾细胞癌和集合管细胞癌。而其它的较少见。由于肾癌具有高度的遗传异质性,现在已发现了很多染色体畸变和基因的突变都可导致肾癌。而且不同类型的肾癌,其致癌基因也不同。如VHL基因突变一般引起透明肾细胞癌,而FH基因则导致乳头状肾细胞癌。近年来,新技术的发展和应用,新的肾癌相关基因的数目也在增加。如最近的外显子组序列分析就找到了一批与透明肾细胞癌有关的基因,包括PBRM1、BAP1、SET2和JARID1c等重要的肾癌相关基因。有些透明肾细胞癌同时带有两个以上基因的突变。随着新技术的出现和研究的深入,越来越多的肾癌基因及各类肾癌标记将会被发现。

Kidney cancer is known to have different histological types with distinct genetic profiles. There are at least 10 subtypes of kidney cancer. The most common subtype is clear cell renal cell carcinoma （RCC） , followed by papillary RCC, chromophobe RCC, and collecting duct carcinoma, etc. Since its high genetic heterogeneity, kidney cancer can be caused by chromosomal abnormalities and mutations in many genes, and each subtype of RCC has its own affected genes. For instance, VHL is associated with clear cell RCC, while FH mutations cause papillary RCC. An increased number of genes were found to be involved in RCCs in the past years. Recent exome - sequencing has revealed a group of genes involved in clear cell RCC tumorigenesis such as PBRM1, BAP1, SETD2, and JARIDlc. Combinational mutations of these genes were also identified in a proportion of clear cell RCCs. With the advent of new genetic technologies, more and more RCC - related genes/markers will be identified.