Identification of a Rat Mammary Tumor Risk Locus That Is Syntenic with the Commonly Amplified 8q12.1 and 8q22.1 Regions in Human Breast Cancer Patients. G3 (Bethesda) 2019 May 07;9(5):1739-1743
Date
03/28/2019Pubmed ID
30914425Pubmed Central ID
PMC6505137DOI
10.1534/g3.118.200873Scopus ID
2-s2.0-85065792535 (requires institutional sign-in at Scopus site) 6 CitationsAbstract
Breast cancer risk is 31% heritable, yet the majority of the underlying risk factors remain poorly defined. Here, we used F2-linkage analysis in a rat mammary tumor model to identify a novel 11.2 Mb modifier locus of tumor incidence and burden on rat chromosome 5 (chr5: 15.4 - 26.6 Mb). Genomic and RNA sequencing analysis identified four differentially expressed candidates: TMEM68, IMPAD1, SDCBP, and RBM12B Analysis of the human syntenic candidate region revealed that SDCBP is in close proximity to a previously reported genetic risk locus for human breast cancer. Moreover, analysis of the candidate genes in The Cancer Genome Atlas (TCGA) revealed that they fall within the commonly amplified 8q12.1 and 8q22.1 regions in human breast cancer patients and are correlated with worse overall survival. Collectively, this study presents novel evidence suggesting that TMEM68, IMPAD1, SDCBP, and RBM12B are potential modifiers of human breast cancer risk and outcome.
Author List
Plasterer C, Tsaih SW, Lemke A, Schilling R, Dwinell M, Rau A, Auer P, Rui H, Flister MJAuthors
Paul L. Auer PhD Professor in the Data Science Institute department at Medical College of WisconsinMelinda R. Dwinell PhD Professor in the Physiology department at Medical College of Wisconsin
Shirng-Wern Tsaih Research Scientist II in the Obstetrics and Gynecology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsBreast Neoplasms
Chromosome Mapping
Chromosomes, Human, Pair 8
Female
Gene Amplification
Gene Expression Profiling
Genetic Predisposition to Disease
Genome, Human
Genomics
High-Throughput Nucleotide Sequencing
Humans
Mammary Neoplasms, Animal
Quantitative Trait Loci
Rats
Tumor Burden