Further confirmation of germline glioma risk variant rs78378222 in TP53 and its implication in tumor tissues via integrative analysis of TCGA data

Details

• Personal Author:
  Ahlbom A ; Albanes D ; Andersson U ; Beane Freeman LE ; Buring JE ; Butler MA ; Carreon T ; Chanock SJ ; Chatterjee N ; Chung CC ; Feychting M ; Fraumeni JF ; Gapstur SM ; Gaziano JM ; Giles GG ; Hallmans G ; Hartge P ; Henriksson R ; Hoffman-Bolton J ; Hoover R ; Inskip PD ; Kitahara CM ; Le Marchand L ; Li S ; Linet MS ; McKean-Cowdin R ; Melin BS ; Michaud D ; Peters U ; Purdue MP ; Rajaraman P ; Rothman N ; Ruder, Avima M. ; Sesso HD ; Severi G ; Stampfer M ; Stevens VL ; Visvanathan K ; Wang SS ; Wang Z ; White E ; Yeager M ; Zeleniuch-Jacquotte A ; Zhang W
• Description:
  We confirmed strong association of rs78378222:A>C [per allele odds ratio [OR] = 3.14; P = 6.48 x 10(-11)], a germline rare single-nucleotide polymorphism (SNP) in TP53, via imputation of a genome-wide association study of glioma (1,856 cases and 4,955 controls). We subsequently performed integrative analyses on the Cancer Genome Atlas (TCGA) data for GBM (glioblastoma multiforme) and LUAD (lung adenocarcinoma). Based on SNP data, we imputed genotypes for rs78378222 and selected individuals carrying rare risk allele (C). Using RNA sequencing data, we observed aberrant transcripts with approximately 3 kb longer than normal for those individuals. Using exome sequencing data, we further showed that loss of haplotype carrying common protective allele (A) occurred somatically in GBM but not in LUAD. Our bioinformatic analysis suggests rare risk allele (C) disrupts mRNA termination, and an allelic loss of a genomic region harboring common protective allele (A) occurs during tumor initiation or progression for glioma. [Description provided by NIOSH]
• Subjects:
  Biomarkers Family Genetics Lung Lung Diseases Neoplasms Nervous System Nervous System Diseases Nucleotides Occupational Health Respiratory System Respiratory Tract Diseases Risk Assessment Risk Factors Safety

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• Keywords:
  Adenocarcinomas Analytical-processes Author Keywords: Glioma Biomedical-engineering Biostatistics Brain-tumors Cancer Cell-morphology Data-processing Families Gene-mutation Genes Genetic-factors Heredity Humans Lung-cancer Malignancy Malignant-neoplasms Morphology Mutation Proteins Rare SNP Ribonucleic-acids Risk-factors TCGA Tissue-disorders TP53 Tumors

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• ISSN:
  1059-7794
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  California ; Georgia ; Hawaii ; Maryland ; Massachusetts ; New York ; Ohio ; OSHA Region 1 ; OSHA Region 10 ; OSHA Region 2 ; OSHA Region 3 ; OSHA Region 4 ; OSHA Region 5 ; OSHA Region 9 ; Rhode Island ; Washington
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  DART - Division of Applied Research and Technology ; DSHEFS - Division of Surveillance, Hazard Evaluations, and Field Studies
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  36
• Issue:
  7
• NIOSHTIC Number:
  nn:20046324
• Citation:
  Hum Mutat 2015 Jul; 36(7):684-688
• Contact Point Address:
  Stephen J. Chanock, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Dr. Rm. 7E412, MSC 9776, Bethesda, MD 20892-9776 (US Postal Service), Rockville, MD 20850 (courier services)
• Email:
  chanocks@mail.nih.gov
• Federal Fiscal Year:
  2015
• Peer Reviewed:
  True
• Source Full Name:
  Human Mutation
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:9e0326d63267b7d421fd9f97dbe64067db6cccba4a64e8599aec35d527f1e6fe26e59080eb802a4cc373e94a1db97c0330f25530d5f79b6e90752d6626732994
• Download URL:
  https://stacks.cdc.gov/view/cdc/201421/cdc_201421_DS1.pdf
• File Type:
  [PDF - 1.26 MB ]