Allelic selection of amplicons in glioblastoma revealed by combining somatic and germline analysis.
Cancer is a disease driven by a combination of inherited risk alleles coupled with the acquisition of somatic mutations, including amplification and deletion of genomic DNA. Potential relationships between the inherited and somatic aspects of the disease have only rarely been examined on a genome-wi...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2010-09-01
|
| Series: | PLoS Genetics |
| Online Access: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1001086&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850236708799381504 |
|---|---|
| author | Thomas LaFramboise Ninad Dewal Katherine Wilkins Itsik Pe'er Matthew L Freedman |
| author_facet | Thomas LaFramboise Ninad Dewal Katherine Wilkins Itsik Pe'er Matthew L Freedman |
| author_sort | Thomas LaFramboise |
| collection | DOAJ |
| description | Cancer is a disease driven by a combination of inherited risk alleles coupled with the acquisition of somatic mutations, including amplification and deletion of genomic DNA. Potential relationships between the inherited and somatic aspects of the disease have only rarely been examined on a genome-wide level. Applying a novel integrative analysis of SNP and copy number measurements, we queried the tumor and normal-tissue genomes of 178 glioblastoma patients from the Cancer Genome Atlas project for preferentially amplified alleles, under the hypothesis that oncogenic germline variants will be selectively amplified in the tumor environment. Selected alleles are revealed by allelic imbalance in amplification across samples. This general approach is based on genetic principles and provides a method for identifying important tumor-related alleles. We find that SNP alleles that are most significantly overrepresented in amplicons tend to occur in genes involved with regulation of kinase and transferase activity, and many of these genes are known contributors to gliomagenesis. The analysis also implicates variants in synapse genes. By incorporating gene expression data, we demonstrate synergy between preferential allelic amplification and expression in DOCK4 and EGFR. Our results support the notion that combining germline and tumor genetic data can identify regions relevant to cancer biology. |
| format | Article |
| id | doaj-art-bf38be6a500740a1ae58f226b7925ebd |
| institution | OA Journals |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2010-09-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-bf38be6a500740a1ae58f226b7925ebd2025-08-20T02:01:54ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042010-09-0169e100108610.1371/journal.pgen.1001086Allelic selection of amplicons in glioblastoma revealed by combining somatic and germline analysis.Thomas LaFramboiseNinad DewalKatherine WilkinsItsik Pe'erMatthew L FreedmanCancer is a disease driven by a combination of inherited risk alleles coupled with the acquisition of somatic mutations, including amplification and deletion of genomic DNA. Potential relationships between the inherited and somatic aspects of the disease have only rarely been examined on a genome-wide level. Applying a novel integrative analysis of SNP and copy number measurements, we queried the tumor and normal-tissue genomes of 178 glioblastoma patients from the Cancer Genome Atlas project for preferentially amplified alleles, under the hypothesis that oncogenic germline variants will be selectively amplified in the tumor environment. Selected alleles are revealed by allelic imbalance in amplification across samples. This general approach is based on genetic principles and provides a method for identifying important tumor-related alleles. We find that SNP alleles that are most significantly overrepresented in amplicons tend to occur in genes involved with regulation of kinase and transferase activity, and many of these genes are known contributors to gliomagenesis. The analysis also implicates variants in synapse genes. By incorporating gene expression data, we demonstrate synergy between preferential allelic amplification and expression in DOCK4 and EGFR. Our results support the notion that combining germline and tumor genetic data can identify regions relevant to cancer biology.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1001086&type=printable |
| spellingShingle | Thomas LaFramboise Ninad Dewal Katherine Wilkins Itsik Pe'er Matthew L Freedman Allelic selection of amplicons in glioblastoma revealed by combining somatic and germline analysis. PLoS Genetics |
| title | Allelic selection of amplicons in glioblastoma revealed by combining somatic and germline analysis. |
| title_full | Allelic selection of amplicons in glioblastoma revealed by combining somatic and germline analysis. |
| title_fullStr | Allelic selection of amplicons in glioblastoma revealed by combining somatic and germline analysis. |
| title_full_unstemmed | Allelic selection of amplicons in glioblastoma revealed by combining somatic and germline analysis. |
| title_short | Allelic selection of amplicons in glioblastoma revealed by combining somatic and germline analysis. |
| title_sort | allelic selection of amplicons in glioblastoma revealed by combining somatic and germline analysis |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1001086&type=printable |
| work_keys_str_mv | AT thomaslaframboise allelicselectionofampliconsinglioblastomarevealedbycombiningsomaticandgermlineanalysis AT ninaddewal allelicselectionofampliconsinglioblastomarevealedbycombiningsomaticandgermlineanalysis AT katherinewilkins allelicselectionofampliconsinglioblastomarevealedbycombiningsomaticandgermlineanalysis AT itsikpeer allelicselectionofampliconsinglioblastomarevealedbycombiningsomaticandgermlineanalysis AT matthewlfreedman allelicselectionofampliconsinglioblastomarevealedbycombiningsomaticandgermlineanalysis |