TY - JOUR

T1 - Germline rearrangements in families with strong family history of glioma and malignant melanoma, colon, and breast cancer

AU - Andersson, Ulrika

AU - Wibom, Carl

AU - Cederquist, Kristina

AU - Aradottir, Steina

AU - Borg, Ake

AU - Armstrong, Georgina N

AU - Shete, Sanjay

AU - Lau, Ching C

AU - Bainbridge, Matthew N

AU - Claus, Elizabeth B

AU - Barnholtz-Sloan, Jill

AU - Lai, Rose

AU - Il'yasova, Dora

AU - Houlston, Richard S

AU - Schildkraut, Joellen

AU - Bernstein, Jonine L

AU - Olson, Sara H

AU - Jenkins, Robert B

AU - Lachance, Daniel H

AU - Wrensch, Margaret

AU - Davis, Faith G

AU - Merrell, Ryan

AU - Johansen, Christoffer

AU - Sadetzki, Siegal

AU - Bondy, Melissa L

AU - Melin, Beatrice S

AU - Gliogene Consortium

N1 - © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.

PY - 2014

Y1 - 2014

N2 - BACKGROUND: Although familial susceptibility to glioma is known, the genetic basis for this susceptibility remains unidentified in the majority of glioma-specific families. An alternative approach to identifying such genes is to examine cancer pedigrees, which include glioma as one of several cancer phenotypes, to determine whether common chromosomal modifications might account for the familial aggregation of glioma and other cancers.METHODS: Germline rearrangements in 146 glioma families (from the Gliogene Consortium; http://www.gliogene.org/) were examined using multiplex ligation-dependent probe amplification. These families all had at least 2 verified glioma cases and a third reported or verified glioma case in the same family or 2 glioma cases in the family with at least one family member affected with melanoma, colon, or breast cancer.The genomic areas covering TP53, CDKN2A, MLH1, and MSH2 were selected because these genes have been previously reported to be associated with cancer pedigrees known to include glioma.RESULTS: We detected a single structural rearrangement, a deletion of exons 1-6 in MSH2, in the proband of one family with 3 cases with glioma and one relative with colon cancer.CONCLUSIONS: Large deletions and duplications are rare events in familial glioma cases, even in families with a strong family history of cancers that may be involved in known cancer syndromes.

AB - BACKGROUND: Although familial susceptibility to glioma is known, the genetic basis for this susceptibility remains unidentified in the majority of glioma-specific families. An alternative approach to identifying such genes is to examine cancer pedigrees, which include glioma as one of several cancer phenotypes, to determine whether common chromosomal modifications might account for the familial aggregation of glioma and other cancers.METHODS: Germline rearrangements in 146 glioma families (from the Gliogene Consortium; http://www.gliogene.org/) were examined using multiplex ligation-dependent probe amplification. These families all had at least 2 verified glioma cases and a third reported or verified glioma case in the same family or 2 glioma cases in the family with at least one family member affected with melanoma, colon, or breast cancer.The genomic areas covering TP53, CDKN2A, MLH1, and MSH2 were selected because these genes have been previously reported to be associated with cancer pedigrees known to include glioma.RESULTS: We detected a single structural rearrangement, a deletion of exons 1-6 in MSH2, in the proband of one family with 3 cases with glioma and one relative with colon cancer.CONCLUSIONS: Large deletions and duplications are rare events in familial glioma cases, even in families with a strong family history of cancers that may be involved in known cancer syndromes.

U2 - 10.1093/neuonc/nou052

DO - 10.1093/neuonc/nou052

M3 - Journal article

C2 - 24723567

VL - 16

SP - 1333

EP - 1340

JO - Neuro-Oncology

JF - Neuro-Oncology

SN - 1522-8517

IS - 10

ER -