Rare and potentially pathogenic variants in hydroxycarboxylic acid receptor genes identified in breast cancer cases

Abstract Background Three genes clustered together on chromosome 12 comprise a group of hydroxycarboxylic acid receptors (HCARs): HCAR1, HCAR2, and HCAR3. These paralogous genes encode different G-protein coupled receptors responsible for detecting glycolytic metabolites and controlling fatty acid o...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Cierla McGuire Sams, Kasey Shepp, Jada Pugh, Madison R. Bishop, Nancy D. Merner
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Breast cancer Hydroxycarboxylic acid receptor G-protein coupled receptor Genetic variants And protein elongation Internal medicine RC31-1245 Genetics QH426-470
Acceso en línea:	https://doaj.org/article/a36021b872c5416e9e8ea45993ee6c7e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a36021b872c5416e9e8ea45993ee6c7e
record_format	dspace
spelling	oai:doaj.org-article:a36021b872c5416e9e8ea45993ee6c7e2021-12-05T12:05:28ZRare and potentially pathogenic variants in hydroxycarboxylic acid receptor genes identified in breast cancer cases10.1186/s12920-021-01126-31755-8794https://doaj.org/article/a36021b872c5416e9e8ea45993ee6c7e2021-12-01T00:00:00Zhttps://doi.org/10.1186/s12920-021-01126-3https://doaj.org/toc/1755-8794Abstract Background Three genes clustered together on chromosome 12 comprise a group of hydroxycarboxylic acid receptors (HCARs): HCAR1, HCAR2, and HCAR3. These paralogous genes encode different G-protein coupled receptors responsible for detecting glycolytic metabolites and controlling fatty acid oxidation. Though better known for regulating lipid metabolism in adipocytes, more recently, HCARs have been functionally associated with breast cancer proliferation/survival; HCAR2 has been described as a tumor suppressor and HCAR1 and HCAR3 as oncogenes. Thus, we sought to identify germline variants in HCAR1, HCAR2, and HCAR3 that could potentially be associated with breast cancer risk. Methods Two different cohorts of breast cancer cases were investigated, the Alabama Hereditary Cancer Cohort and The Cancer Genome Atlas, which were analyzed through nested PCRs/Sanger sequencing and whole-exome sequencing, respectively. All datasets were screened for rare, non-synonymous coding variants. Results Variants were identified in both breast cancer cohorts, some of which appeared to be associated with breast cancer BC risk, including HCAR1 c.58C > G (p.P20A), HCAR2 c.424C > T (p.R142W), HCAR2 c.517_518delinsAC (p.G173T), HCAR2 c.1036A > G (p.M346V), HCAR2 c.1086_1090del (p.P363Nfs26), HCAR3 c.560G > A (p.R187Q), and HCAR3 c.1117delC (p.Q373Kfs82). Additionally, HCAR2 c.515C > T (p.S172L), a previously identified loss-of-function variant, was identified. Conclusions Due to the important role of HCARs in breast cancer, it is vital to understand how these genetic variants play a role in breast cancer risk and proliferation and their consequences on treatment strategies. Additional studies will be needed to validate these findings. Nevertheless, the identification of these potentially pathogenic variants supports the need to investigate their functional consequences.Cierla McGuire SamsKasey SheppJada PughMadison R. BishopNancy D. MernerBMCarticleBreast cancerHydroxycarboxylic acid receptorG-protein coupled receptorGenetic variantsAnd protein elongationInternal medicineRC31-1245GeneticsQH426-470ENBMC Medical Genomics, Vol 14, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Breast cancer Hydroxycarboxylic acid receptor G-protein coupled receptor Genetic variants And protein elongation Internal medicine RC31-1245 Genetics QH426-470
spellingShingle	Breast cancer Hydroxycarboxylic acid receptor G-protein coupled receptor Genetic variants And protein elongation Internal medicine RC31-1245 Genetics QH426-470 Cierla McGuire Sams Kasey Shepp Jada Pugh Madison R. Bishop Nancy D. Merner Rare and potentially pathogenic variants in hydroxycarboxylic acid receptor genes identified in breast cancer cases
description	Abstract Background Three genes clustered together on chromosome 12 comprise a group of hydroxycarboxylic acid receptors (HCARs): HCAR1, HCAR2, and HCAR3. These paralogous genes encode different G-protein coupled receptors responsible for detecting glycolytic metabolites and controlling fatty acid oxidation. Though better known for regulating lipid metabolism in adipocytes, more recently, HCARs have been functionally associated with breast cancer proliferation/survival; HCAR2 has been described as a tumor suppressor and HCAR1 and HCAR3 as oncogenes. Thus, we sought to identify germline variants in HCAR1, HCAR2, and HCAR3 that could potentially be associated with breast cancer risk. Methods Two different cohorts of breast cancer cases were investigated, the Alabama Hereditary Cancer Cohort and The Cancer Genome Atlas, which were analyzed through nested PCRs/Sanger sequencing and whole-exome sequencing, respectively. All datasets were screened for rare, non-synonymous coding variants. Results Variants were identified in both breast cancer cohorts, some of which appeared to be associated with breast cancer BC risk, including HCAR1 c.58C > G (p.P20A), HCAR2 c.424C > T (p.R142W), HCAR2 c.517_518delinsAC (p.G173T), HCAR2 c.1036A > G (p.M346V), HCAR2 c.1086_1090del (p.P363Nfs26), HCAR3 c.560G > A (p.R187Q), and HCAR3 c.1117delC (p.Q373Kfs82). Additionally, HCAR2 c.515C > T (p.S172L), a previously identified loss-of-function variant, was identified. Conclusions Due to the important role of HCARs in breast cancer, it is vital to understand how these genetic variants play a role in breast cancer risk and proliferation and their consequences on treatment strategies. Additional studies will be needed to validate these findings. Nevertheless, the identification of these potentially pathogenic variants supports the need to investigate their functional consequences.
format	article
author	Cierla McGuire Sams Kasey Shepp Jada Pugh Madison R. Bishop Nancy D. Merner
author_facet	Cierla McGuire Sams Kasey Shepp Jada Pugh Madison R. Bishop Nancy D. Merner
author_sort	Cierla McGuire Sams
title	Rare and potentially pathogenic variants in hydroxycarboxylic acid receptor genes identified in breast cancer cases
title_short	Rare and potentially pathogenic variants in hydroxycarboxylic acid receptor genes identified in breast cancer cases
title_full	Rare and potentially pathogenic variants in hydroxycarboxylic acid receptor genes identified in breast cancer cases
title_fullStr	Rare and potentially pathogenic variants in hydroxycarboxylic acid receptor genes identified in breast cancer cases
title_full_unstemmed	Rare and potentially pathogenic variants in hydroxycarboxylic acid receptor genes identified in breast cancer cases
title_sort	rare and potentially pathogenic variants in hydroxycarboxylic acid receptor genes identified in breast cancer cases
publisher	BMC
publishDate	2021
url	https://doaj.org/article/a36021b872c5416e9e8ea45993ee6c7e
work_keys_str_mv	AT cierlamcguiresams rareandpotentiallypathogenicvariantsinhydroxycarboxylicacidreceptorgenesidentifiedinbreastcancercases AT kaseyshepp rareandpotentiallypathogenicvariantsinhydroxycarboxylicacidreceptorgenesidentifiedinbreastcancercases AT jadapugh rareandpotentiallypathogenicvariantsinhydroxycarboxylicacidreceptorgenesidentifiedinbreastcancercases AT madisonrbishop rareandpotentiallypathogenicvariantsinhydroxycarboxylicacidreceptorgenesidentifiedinbreastcancercases AT nancydmerner rareandpotentiallypathogenicvariantsinhydroxycarboxylicacidreceptorgenesidentifiedinbreastcancercases
_version_	1718372275387891712

Rare and potentially pathogenic variants in hydroxycarboxylic acid receptor genes identified in breast cancer cases

Ejemplares similares