In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 8_Supplement ( 2013-04-15), p. 4207-4207
Abstract:
Background: Gliomas are primary malignant brain tumors with significant morbidity and mortality. Single nucleotide polymorphisms (SNPs) mapped to 8q24 have been shown to be associated with glioma development. Recently, we identified seven SNPs (through tag SNP genotyping/imputation, pooled next-generation sequencing using long-range PCR, and validation SNP genotyping) that are highly associated with the risk of developing glioma. After stratifying by histologic and tumor subtype, one SNP, rs55705857, in the 8q24.21 region near CCDC26 was significantly associated with oligodendroglial tumors and IDH mutated astrocytic gliomas with high odds ratios (ORs ∼6.0) (Jenkins et al. Nature Genet. 44:1122;2012). By array comparative genomic hybridization (aCGH), a significant proportion of oligodendroglial tumors and IDH mutated astrocytomas have been shown to duplicate 8q24 (Kitange et al., Genes Chr Cancer 42:68;2005; Nousmehr et al. Cancer Cell 17:510;2010). We were interested in learning if the germline risk allele of rs55705857 is associated with gliomas that duplicate 8q24. We were also interested in learning if the risk allele is preferentially gained in gliomas that duplicate 8q24. Methods: We performed aCGH on 217 tumor samples. rs55705857 germline genotype was available on 120 of the patients; of which 30 carried the risk (G) allele. In addition, we sequenced the rs55805857 region in 48 gliomas, 15 of which exhibited gain or duplication of chromosome 8, 8q, or 8q24. The ratio of the Sanger-sequencing peak heights at and around rs55705857 was used to determine which allele (risk or wild-type) was gained. Results: All 15 duplications included rs55705857 and the immediately adjacent regions. Of the 30 patients who carried the germline risk (G) allele for rs55707857, 8 (26.7%) exhibited duplication of 8q24 upon aCGH analysis of their glioma. Of the 90 patients who only carried the wild-type (A) allele, 7 (7.5%) exhibited duplications of 8q24 upon aCGH analysis of their glioma. This difference in proportion is statistically significant (p=0.024, Fischer exact test). Of the 15 tumors with duplication of 8q24, 8 came from patients who were germline rs55705857 heterozygotes (AG). Of these 8 germline heterozygotes with duplication of 8q24, 4 gained the risk (G) allele, 2 gained the wild-type (A) allele and 2 exhibited gain of both alleles in their tumor specimens. Conclusions: While the results require replication, our data suggest that carrying the risk allele for rs55705857 predisposes to the development of gliomas that subsequently duplicate 8q24. However, gliomas with duplication of 8q24 do not preferentially gain the risk rs55705857 allele. This result implies that, while the duplication always includes the rs55705857 region, the risk allele or region is not the direct target of the duplication. Citation Format: Amanda L. Rynearson, Kirsten A. Schowalter, Stephanie R. Fink, Thomas M. Kollmeyer, Chandralekha Halder, Gobinda Sarkar, Alissa A. Caron, Rachel A. Pauley, Daniel H. Lachance, Brian Patrick O'Neill, Robert B. Jenkins. The germline rs55705857 risk allele is not preferentially gained in gliomas with 8q24 duplication. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4207. doi:10.1158/1538-7445.AM2013-4207
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2013-4207
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2013
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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