{"title":"基因组时代儿童癌症的遗传易感性。","authors":"Sharon E Plon, Philip J Lupo","doi":"10.1146/annurev-genom-083118-015415","DOIUrl":null,"url":null,"abstract":"<p><p>Developments over the past five years have significantly advanced our ability to use genome-scale analyses-including high-density genotyping, transcriptome sequencing, exome sequencing, and genome sequencing-to identify the genetic basis of childhood cancer. This article reviews several key results from an expanding number of genomic studies of pediatric cancer: (<i>a</i>) Histopathologic subtypes of cancers can be associated with a high incidence of germline predisposition, (<i>b</i>) neurodevelopmental disorders or highly penetrant cancer predisposition syndromes can result from specific patterns of variation in genes encoding the SMARC family of chromatin remodelers, (<i>c</i>) genome-wide association studies with relatively small pediatric cancer cohorts have successfully identified single-nucleotide polymorphisms with large effect sizes and provided insight into population differences in cancer risk, and (<i>d</i>) multiple exome or genome analyses of unselected childhood cancer cohorts have yielded a 7-10% incidence of pathogenic variants in cancer predisposition genes. This work supports the increasing use of genomic sequencing in the care of pediatric cancer patients and at-risk family members.</p>","PeriodicalId":8231,"journal":{"name":"Annual review of genomics and human genetics","volume":"20 ","pages":"241-263"},"PeriodicalIF":7.7000,"publicationDate":"2019-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1146/annurev-genom-083118-015415","citationCount":"25","resultStr":"{\"title\":\"Genetic Predisposition to Childhood Cancer in the Genomic Era.\",\"authors\":\"Sharon E Plon, Philip J Lupo\",\"doi\":\"10.1146/annurev-genom-083118-015415\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Developments over the past five years have significantly advanced our ability to use genome-scale analyses-including high-density genotyping, transcriptome sequencing, exome sequencing, and genome sequencing-to identify the genetic basis of childhood cancer. This article reviews several key results from an expanding number of genomic studies of pediatric cancer: (<i>a</i>) Histopathologic subtypes of cancers can be associated with a high incidence of germline predisposition, (<i>b</i>) neurodevelopmental disorders or highly penetrant cancer predisposition syndromes can result from specific patterns of variation in genes encoding the SMARC family of chromatin remodelers, (<i>c</i>) genome-wide association studies with relatively small pediatric cancer cohorts have successfully identified single-nucleotide polymorphisms with large effect sizes and provided insight into population differences in cancer risk, and (<i>d</i>) multiple exome or genome analyses of unselected childhood cancer cohorts have yielded a 7-10% incidence of pathogenic variants in cancer predisposition genes. This work supports the increasing use of genomic sequencing in the care of pediatric cancer patients and at-risk family members.</p>\",\"PeriodicalId\":8231,\"journal\":{\"name\":\"Annual review of genomics and human genetics\",\"volume\":\"20 \",\"pages\":\"241-263\"},\"PeriodicalIF\":7.7000,\"publicationDate\":\"2019-08-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1146/annurev-genom-083118-015415\",\"citationCount\":\"25\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annual review of genomics and human genetics\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1146/annurev-genom-083118-015415\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2019/5/13 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annual review of genomics and human genetics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1146/annurev-genom-083118-015415","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2019/5/13 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
Genetic Predisposition to Childhood Cancer in the Genomic Era.
Developments over the past five years have significantly advanced our ability to use genome-scale analyses-including high-density genotyping, transcriptome sequencing, exome sequencing, and genome sequencing-to identify the genetic basis of childhood cancer. This article reviews several key results from an expanding number of genomic studies of pediatric cancer: (a) Histopathologic subtypes of cancers can be associated with a high incidence of germline predisposition, (b) neurodevelopmental disorders or highly penetrant cancer predisposition syndromes can result from specific patterns of variation in genes encoding the SMARC family of chromatin remodelers, (c) genome-wide association studies with relatively small pediatric cancer cohorts have successfully identified single-nucleotide polymorphisms with large effect sizes and provided insight into population differences in cancer risk, and (d) multiple exome or genome analyses of unselected childhood cancer cohorts have yielded a 7-10% incidence of pathogenic variants in cancer predisposition genes. This work supports the increasing use of genomic sequencing in the care of pediatric cancer patients and at-risk family members.
期刊介绍:
Since its inception in 2000, the Annual Review of Genomics and Human Genetics has been dedicated to showcasing significant developments in genomics as they pertain to human genetics and the human genome. The journal emphasizes genomic technology, genome structure and function, genetic modification, human variation and population genetics, human evolution, and various aspects of human genetic diseases, including individualized medicine.