Dataset Information

Targeted sequencing in chromosome 17q linkage region identifies familial glioma candidates in the Gliogene Consortium.

ABSTRACT: Glioma is a rare, but highly fatal, cancer that accounts for the majority of malignant primary brain tumors. Inherited predisposition to glioma has been consistently observed within non-syndromic families. Our previous studies, which involved non-parametric and parametric linkage analyses, both yielded significant linkage peaks on chromosome 17q. Here, we use data from next generation and Sanger sequencing to identify familial glioma candidate genes and variants on chromosome 17q for further investigation. We applied a filtering schema to narrow the original list of 4830 annotated variants down to 21 very rare (<0.1% frequency), non-synonymous variants. Our findings implicate the MYO19 and KIF18B genes and rare variants in SPAG9 and RUNDC1 as candidates worthy of further investigation. Burden testing and functional studies are planned.

SUBMITTER: Jalali A

PROVIDER: S-EPMC4317686 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Targeted sequencing in chromosome 17q linkage region identifies familial glioma candidates in the Gliogene Consortium.

Jalali Ali A Amirian E Susan ES Bainbridge Matthew N MN Armstrong Georgina N GN Liu Yanhong Y Tsavachidis Spyros S Jhangiani Shalini N SN Plon Sharon E SE Lau Ching C CC Claus Elizabeth B EB Barnholtz-Sloan Jill S JS Il'yasova Dora D Schildkraut Joellen J Ali-Osman Francis F Sadetzki Siegal S Johansen Christoffer C Houlston Richard S RS Jenkins Robert B RB Lachance Daniel D Olson Sara H SH Bernstein Jonine L JL Merrell Ryan T RT Wrensch Margaret R MR Davis Faith G FG Lai Rose R Shete Sanjay S Aldape Kenneth K Amos Christopher I CI Muzny Donna M DM Gibbs Richard A RA Melin Beatrice S BS Bondy Melissa L ML

Scientific reports 20150205

Glioma is a rare, but highly fatal, cancer that accounts for the majority of malignant primary brain tumors. Inherited predisposition to glioma has been consistently observed within non-syndromic families. Our previous studies, which involved non-parametric and parametric linkage analyses, both yielded significant linkage peaks on chromosome 17q. Here, we use data from next generation and Sanger sequencing to identify familial glioma candidate genes and variants on chromosome 17q for further inv ...[more]

PMID: 25652157

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Project description:BackgroundWhile certain inherited syndromes (e.g. Neurofibromatosis or Li-Fraumeni) are associated with an increased risk of glioma, most familial gliomas are non-syndromic. This study describes the demographic and clinical characteristics of the largest series of non-syndromic glioma families ascertained from 14 centres in the United States (US), Europe and Israel as part of the Gliogene Consortium.MethodsFamilies with 2 or more verified gliomas were recruited between January 2007 and February 2011. Distributions of demographic characteristics and clinical variables of gliomas in the families were described based on information derived from personal questionnaires.FindingsThe study population comprised 841 glioma patients identified in 376 families (9797 individuals). There were more cases of glioma among males, with a male to female ratio of 1.25. In most families (83%), 2 gliomas were reported, with 3 and 4 gliomas in 13% and 3% of the families, respectively. For families with 2 gliomas, 57% were among 1st-degree relatives, and 31.5% among 2nd-degree relatives. Overall, the mean (±standard deviation [SD]) diagnosis age was 49.4 (±18.7) years. In 48% of families with 2 gliomas, at least one was diagnosed at <40y, and in 12% both were diagnosed under 40y of age. Most of these families (76%) had at least one grade IV glioblastoma multiforme (GBM), and in 32% both cases were grade IV gliomas. The most common glioma subtype was GBM (55%), followed by anaplastic astrocytoma (10%) and oligodendroglioma (8%). Individuals with grades I-II were on average 17y younger than those with grades III-IV.InterpretationFamilial glioma cases are similar to sporadic cases in terms of gender distribution, age, morphology and grade. Most familial gliomas appear to comprise clusters of two cases suggesting low penetrance, and that the risk of developing additional gliomas is probably low. These results should be useful in the counselling and clinical management of individuals with a family history of glioma.

Dataset Information

Targeted sequencing in chromosome 17q linkage region identifies familial glioma candidates in the Gliogene Consortium.

Publications

Targeted sequencing in chromosome 17q linkage region identifies familial glioma candidates in the Gliogene Consortium.

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