Inherited mutations in cancer susceptibility genes are common among survivors of breast cancer who develop therapy-related leukemia

被引：132

作者：

Churpek, Jane E. ^{[1
,2
,3
]}

Marquez, Rafael ^{[2
]}

Neistadt, Barbara ^{[2
]}

Claussen, Kimberly ^{[2
]}

Lee, Ming K. ^{[4
]}

Churpek, Matthew M. ^{[2
,5
]}

Huo, Dezheng ^{[5
]}

Weiner, Howard ^{[2
]}

Bannerjee, Mekhala ^{[2
]}

Godley, Lucy A. ^{[1
,2
,3
]}

Le Beau, Michelle M. ^{[2
,3
]}

Pritchard, Colin C. ^{[6
]}

Walsh, Tom ^{[4
]}

King, Mary-Claire ^{[4
]}

Olopade, Olufunmilayo I. ^{[1
,2
,3
]}

Larson, Richard A. ^{[2
,3
]}

机构：

[1] Univ Chicago, Ctr Clin Canc Genet, Chicago, IL 60635 USA

[2] Univ Chicago, Dept Med, Chicago, IL 60637 USA

[3] Univ Chicago, Ctr Comprehens Canc, Chicago, IL 60635 USA

[4] Univ Washington, Sch Med, Dept Med, Div Med Genet, Seattle, WA 98195 USA

[5] Univ Chicago, Dept Hlth Studies, Chicago, IL 60635 USA

[6] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA

来源：

CANCER | 2016年 / 122卷 / 02期

基金：

美国国家卫生研究院;

关键词：

breast cancer; inherited; leukemia; therapy-related; ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; BRCA2; MUTATIONS; ADJUVANT BREAST; PREVALENCE; RISK; CARRIERS; CAPTURE; ADULTS; WOMEN;

D O I：

10.1002/cncr.29615

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

BACKGROUNDRisk factors for the development of therapy-related leukemia (TRL), an often lethal late complication of cytotoxic therapy, remain poorly understood and may differ for survivors of different malignancies. Survivors of breast cancer (BC) now account for the majority of TRL cases, making the study of TRL risk factors in this population a priority. METHODSSubjects with TRL after cytotoxic therapy for a primary BC were identified from the TRL registry at The University of Chicago. Those with an available germline DNA sample were screened with a comprehensive gene panel covering known inherited BC susceptibility genes. Clinical and TRL characteristics of all subjects and those with identified germline mutations were described. RESULTSNineteen of 88 survivors of BC with TRL (22%) had an additional primary cancer and 40 of the 70 survivors with an available family history (57%) had a close relative with breast, ovarian, or pancreatic cancer. Of the 47 subjects with available DNA, 10 (21%) were found to carry a deleterious inherited mutation in BRCA1 (3 subjects; 6%), BRCA2 (2 subjects; 4%), TP53 (tumor protein p53) (3 subjects; 6%), CHEK2 (checkpoint kinase 2) (1 subject; 2%), and PALB2 (partner and localizer of BRCA2) (1 subject; 2%). CONCLUSIONSSurvivors of BC with TRL have personal and family histories suggestive of inherited cancer susceptibility and frequently carry germline mutations in BC susceptibility genes. The data from the current study support the role of these genes in TRL risk and suggest that long-term follow-up studies of women with germline mutations who are treated for BC and functional studies of the effects of heterozygous mutations in these genes on bone marrow function after cytotoxic exposures are warranted. Cancer 2016;122:304-311. (c) 2015 American Cancer Society. Inherited mutations in cancer susceptibility genes are common in survivors of breast cancer who develop therapy-related leukemia. Long-term follow-up studies of women with germline cancer susceptibility gene mutations who are treated for breast cancer and functional studies of the effects of heterozygous mutations in these genes on bone marrow function after cytotoxic exposures are warranted.

引用

页码：304 / 311

页数：8

共 33 条

[21] Validation and Implementation of Targeted Capture and Sequencing for the Detection of Actionable Mutation, Copy Number Variation, and Gene Rearrangement in Clinical Cancer Specimens [J].