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

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...

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Main Authors: Cody Plasterer, Shirng-Wern Tsaih, Angela Lemke, Rebecca Schilling, Melinda Dwinell, Andrea Rau, Paul Auer, Hallgeir Rui, Michael J. Flister
Format: Article
Language:English
Published: Oxford University Press 2019-05-01
Series:G3: Genes, Genomes, Genetics
Subjects:
Online Access:http://g3journal.org/lookup/doi/10.1534/g3.118.200873
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author Cody Plasterer
Shirng-Wern Tsaih
Angela Lemke
Rebecca Schilling
Melinda Dwinell
Andrea Rau
Paul Auer
Hallgeir Rui
Michael J. Flister
author_facet Cody Plasterer
Shirng-Wern Tsaih
Angela Lemke
Rebecca Schilling
Melinda Dwinell
Andrea Rau
Paul Auer
Hallgeir Rui
Michael J. Flister
author_sort Cody Plasterer
collection DOAJ
description 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.
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spelling doaj.art-299bb2060c844500b407e1f181aa14af2022-12-21T19:20:50ZengOxford University PressG3: Genes, Genomes, Genetics2160-18362019-05-01951739174310.1534/g3.118.20087340Identification of a Rat Mammary Tumor Risk Locus That Is Syntenic with the Commonly Amplified 8q12.1 and 8q22.1 Regions in Human Breast Cancer PatientsCody PlastererShirng-Wern TsaihAngela LemkeRebecca SchillingMelinda DwinellAndrea RauPaul AuerHallgeir RuiMichael J. FlisterBreast 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.http://g3journal.org/lookup/doi/10.1534/g3.118.200873breast cancerriskincidenceoutcomeTCGA
spellingShingle Cody Plasterer
Shirng-Wern Tsaih
Angela Lemke
Rebecca Schilling
Melinda Dwinell
Andrea Rau
Paul Auer
Hallgeir Rui
Michael J. Flister
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: Genes, Genomes, Genetics
breast cancer
risk
incidence
outcome
TCGA
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic breast cancer
risk
incidence
outcome
TCGA
url http://g3journal.org/lookup/doi/10.1534/g3.118.200873
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