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Germline Mutations in Predisposition Genes in Pediatric Cancer

by Walsh, Michael F , Wilson, Richard K , Wilkinson, Mark R , Nuccio, Regina , Quinn, Emily , Shurtleff, Sheila A , Ma, Xiaotu , Wang, Shuoguo , McGee, Rose B , Weaver, Meaghann S , Easton, John , Pappo, Alberto S , Vadodaria, Bhavin , Zhang, Jinghui , Mardis, Elaine R , Wu, Gang , Ding, Li , Nichols, Kim E , Yergeau, Donald A , Edmonson, Michael N , Downing, James R , Rusch, Michael , Gajjar, Amar , Gruber, Tanja A , Zhou, Xin , Patel, Aman , Pui, Ching-Hon , Chen, Xiang , Ellison, David W , Becksfort, Jared B , Hedges, Dale , Hines-Dowell, Stacy

in Adenomatous polyposis coli / Adolescent / Adolescents / Autism / Autistic Disorder - genetics / BRCA2 protein / Cancer / Child / Children / Children & youth / Computer applications / Data processing / Female / Genes / Genes, Dominant / Genes, Neoplasm / Genetic counseling / Genetic Predisposition to Disease / Genome, Human / Genomes / Germ-Line Mutation / Humans / Male / Mutation / Neoplasms - genetics / Nucleotide sequence / p53 Protein / Pathogenesis / Pathogenicity / Pediatrics / Runx1 protein / SEER Program / Sequence Analysis, DNA - methods / Tumor suppressor genes / Tumorigenesis / Young Adult

2015

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Germline Mutations in Predisposition Genes in Pediatric Cancer

2015

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2015

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Journal Article

Germline Mutations in Predisposition Genes in Pediatric Cancer

Walsh, Michael F,

Wilson, Richard K,

Wilkinson, Mark R,

Nuccio, Regina,

Quinn, Emily,

Shurtleff, Sheila A,

Ma, Xiaotu,

Wang, Shuoguo,

McGee, Rose B,

Weaver, Meaghann S,

Easton, John,

Pappo, Alberto S,

Vadodaria, Bhavin,

Zhang, Jinghui,

Mardis, Elaine R,

Wu, Gang,

Ding, Li,

Nichols, Kim E,

Yergeau, Donald A,

Edmonson, Michael N,

Downing, James R,

Rusch, Michael,

Gajjar, Amar,

Gruber, Tanja A,

Zhou, Xin,

Patel, Aman,

Pui, Ching-Hon,

Chen, Xiang,

Ellison, David W,

Becksfort, Jared B,

Hedges, Dale,

Hines-Dowell, Stacy

2015

Overview

A constitutive mutation in a cancer-susceptibility gene can have implications for clinical treatment and genetic counseling of family members. This study involving 1120 children and adolescents showed that 95 (8.5%) had such a mutation. The frequency of germline mutations in cancer-predisposition genes in children and adolescents with cancer and the implications of such mutations are largely unknown. Previous studies have relied mainly on candidate-gene approaches, which are, by design, limited. To better determine the contribution of germline predisposition mutations to childhood cancer, we used next-generation sequencing, including whole-genome and whole-exome sequencing, to analyze the genomes of 1120 children and adolescents with cancer. We describe the prevalence and spectrum of germline variants among 565 cancer-associated genes, with an emphasis on the analysis of 60 genes that have been associated with autosomal dominant cancer-predisposition syndromes. We . . .

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Publisher

Massachusetts Medical Society

Subject

Adenomatous polyposis coli

/ Adolescent

/ Adolescents

/ Autism

/ Autistic Disorder - genetics

/ BRCA2 protein

/ Cancer