Mutational signatures among young-onset testicular cancers

Abstract Background Incidence of testicular cancer is highest among young adults and has been increasing dramatically for men born since 1945. This study aimed to elucidate the factors driving this trend by investigating differences in mutational signatures by age of onset. Methods We retrieved soma...

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Autores principales:	Nicole E. Mealey, Dylan E. O’Sullivan, Cheryl E. Peters, Daniel Y. C. Heng, Darren R. Brenner
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Mutational signatures Testicular neoplasms Young-onset Genomics Somatic mutations Internal medicine RC31-1245 Genetics QH426-470
Acceso en línea:	https://doaj.org/article/b300a6f7c3ce458089ca8c690cc00b74
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spelling	oai:doaj.org-article:b300a6f7c3ce458089ca8c690cc00b742021-11-28T12:06:04ZMutational signatures among young-onset testicular cancers10.1186/s12920-021-01121-81755-8794https://doaj.org/article/b300a6f7c3ce458089ca8c690cc00b742021-11-01T00:00:00Zhttps://doi.org/10.1186/s12920-021-01121-8https://doaj.org/toc/1755-8794Abstract Background Incidence of testicular cancer is highest among young adults and has been increasing dramatically for men born since 1945. This study aimed to elucidate the factors driving this trend by investigating differences in mutational signatures by age of onset. Methods We retrieved somatic variant and clinical data pertaining to 135 testicular tumors from The Cancer Genome Atlas. We compared mutational load, prevalence of specific mutated genes, mutation types, and mutational signatures between age of onset groups (< 30 years, 30–39 years, ≥ 40 years) after adjusting for subtype. A recursively partitioned mixture model was utilized to characterize combinations of signatures among the young-onset cases. Results Mutational load was significantly higher among older-onset tumors (p < 0.05). There were no highly prevalent driver mutations among young-onset tumors. Mutated genes and types of nucleotide mutations were not significantly different by age group (p > 0.05). Signatures 1, 8 and 29 were more common among young-onset tumors, while signatures 11 and 16 had higher prevalence among older-onset tumors (p < 0.05). Among young-onset tumors, clustering of signatures resulted in four distinct tumor classes. Conclusions Signature contributions differ by age with signatures 1, 8 and 29 were more common among younger-onset tumors. While these signatures are connected with endogenous deamination of 5-methylcytosine, late replication errors and chewing tobacco, respectively, additional research is needed to further elucidate the etiology of young-onset testicular cancer. Large studies of mutational signatures among young-onset patients are required to understand epidemiologic trends as well as inform targeted prevention and treatment strategies.Nicole E. MealeyDylan E. O’SullivanCheryl E. PetersDaniel Y. C. HengDarren R. BrennerBMCarticleMutational signaturesTesticular neoplasmsYoung-onsetGenomicsSomatic mutationsInternal medicineRC31-1245GeneticsQH426-470ENBMC Medical Genomics, Vol 14, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Mutational signatures Testicular neoplasms Young-onset Genomics Somatic mutations Internal medicine RC31-1245 Genetics QH426-470
spellingShingle	Mutational signatures Testicular neoplasms Young-onset Genomics Somatic mutations Internal medicine RC31-1245 Genetics QH426-470 Nicole E. Mealey Dylan E. O’Sullivan Cheryl E. Peters Daniel Y. C. Heng Darren R. Brenner Mutational signatures among young-onset testicular cancers
description	Abstract Background Incidence of testicular cancer is highest among young adults and has been increasing dramatically for men born since 1945. This study aimed to elucidate the factors driving this trend by investigating differences in mutational signatures by age of onset. Methods We retrieved somatic variant and clinical data pertaining to 135 testicular tumors from The Cancer Genome Atlas. We compared mutational load, prevalence of specific mutated genes, mutation types, and mutational signatures between age of onset groups (< 30 years, 30–39 years, ≥ 40 years) after adjusting for subtype. A recursively partitioned mixture model was utilized to characterize combinations of signatures among the young-onset cases. Results Mutational load was significantly higher among older-onset tumors (p < 0.05). There were no highly prevalent driver mutations among young-onset tumors. Mutated genes and types of nucleotide mutations were not significantly different by age group (p > 0.05). Signatures 1, 8 and 29 were more common among young-onset tumors, while signatures 11 and 16 had higher prevalence among older-onset tumors (p < 0.05). Among young-onset tumors, clustering of signatures resulted in four distinct tumor classes. Conclusions Signature contributions differ by age with signatures 1, 8 and 29 were more common among younger-onset tumors. While these signatures are connected with endogenous deamination of 5-methylcytosine, late replication errors and chewing tobacco, respectively, additional research is needed to further elucidate the etiology of young-onset testicular cancer. Large studies of mutational signatures among young-onset patients are required to understand epidemiologic trends as well as inform targeted prevention and treatment strategies.
format	article
author	Nicole E. Mealey Dylan E. O’Sullivan Cheryl E. Peters Daniel Y. C. Heng Darren R. Brenner
author_facet	Nicole E. Mealey Dylan E. O’Sullivan Cheryl E. Peters Daniel Y. C. Heng Darren R. Brenner
author_sort	Nicole E. Mealey
title	Mutational signatures among young-onset testicular cancers
title_short	Mutational signatures among young-onset testicular cancers
title_full	Mutational signatures among young-onset testicular cancers
title_fullStr	Mutational signatures among young-onset testicular cancers
title_full_unstemmed	Mutational signatures among young-onset testicular cancers
title_sort	mutational signatures among young-onset testicular cancers
publisher	BMC
publishDate	2021
url	https://doaj.org/article/b300a6f7c3ce458089ca8c690cc00b74
work_keys_str_mv	AT nicoleemealey mutationalsignaturesamongyoungonsettesticularcancers AT dylaneosullivan mutationalsignaturesamongyoungonsettesticularcancers AT cherylepeters mutationalsignaturesamongyoungonsettesticularcancers AT danielycheng mutationalsignaturesamongyoungonsettesticularcancers AT darrenrbrenner mutationalsignaturesamongyoungonsettesticularcancers
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Mutational signatures among young-onset testicular cancers

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