肾细胞癌患者种系变异中的跨种族差异。

Trans-ethnic variation in germline variants of patients with renal cell carcinoma.

作者信息

Abou Alaiwi Sarah, Nassar Amin H, Adib Elio, Groha Stefan M, Akl Elie W, McGregor Bradley A, Esplin Edward D, Yang Shan, Hatchell Kathryn, Fusaro Vincent, Nielsen Sarah, Kwiatkowski David J, Sonpavde Guru P, Pomerantz Mark, Garber Judy E, Freedman Matthew L, Rana Huma Q, Gusev Alexander, Choueiri Toni K

机构信息

Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Division of Pulmonary and Critical Care Medicine and Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

出版信息

Cell Rep. 2021 Mar 30;34(13):108926. doi: 10.1016/j.celrep.2021.108926.

DOI:10.1016/j.celrep.2021.108926

PMID:33789101

Abstract

Prior studies of the renal cell carcinoma (RCC) germline landscape investigated predominantly patients of European ancestry. We examine the frequency of germline pathogenic and likely pathogenic (P/LP) variants in 1,829 patients with RCC from various ancestries. Overall, P/LP variants are found in 17% of patients, among whom 10.3% harbor one or more clinically actionable variants with potential preventive or therapeutic utility. Patients of African ancestry with RCC harbor significantly more P/LP variants in FH compared to patients of non-African ancestry with RCC and African controls from the Genome Aggregation Database (gnomAD). Patients of non-African ancestry have significantly more P/LP variants in CHEK2 compared to patients of African ancestry with RCC and non-Finnish Europeans controls. Non-Africans with RCC have more actionable variants compared to Africans with RCC. This work helps understand the underlying biological differences in RCC between Africans and non-Africans and paves the way to more comprehensive genomic characterization of underrepresented populations.

摘要

先前对肾细胞癌（RCC）种系图谱的研究主要调查的是欧洲血统的患者。我们研究了1829例不同血统的RCC患者中种系致病性和可能致病性（P/LP）变异的频率。总体而言，17%的患者存在P/LP变异，其中10.3%携带一种或多种具有潜在预防或治疗效用的临床可操作变异。与来自基因组聚合数据库（gnomAD）的非非洲血统RCC患者和非洲对照相比，非洲血统的RCC患者在FH基因中携带的P/LP变异显著更多。与非洲血统的RCC患者和非芬兰欧洲对照相比，非非洲血统的患者在CHEK2基因中携带的P/LP变异显著更多。与非洲RCC患者相比，非非洲RCC患者有更多可操作的变异。这项工作有助于了解非洲人和非非洲人RCC潜在的生物学差异，并为对代表性不足人群进行更全面的基因组特征分析铺平道路。