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A pilot genome-wide association study shows genomic variants enriched in the non-tumor cells of patients with well-differentiated neuroendocrine tumors of the ileum.

Publication ,  Journal Article
Walsh, KM; Choi, M; Oberg, K; Kulke, MH; Yao, JC; Wu, C; Jurkiewicz, M; Hsu, L-I; Hooshmand, SM; Hassan, M; Janson, ET; Cunningham, JL ...
Published in: Endocr Relat Cancer
February 2011

Genetic studies of midgut carcinoid cancer have exclusively focused on genomic changes of the tumor cells. We investigated the role of constitutional genetic polymorphisms in predisposing individuals to ileal carcinoids. In all, 239 cases and 110 controls were collected from three institutions: the Uppsala University Hospital; the Dana-Farber Cancer Institute; and the MD Anderson Cancer Center, and were genotyped using microarrays assaying >300 000 single nucleotide polymorphisms. Association with rs2208059 in KIF16B approached statistical significance (Mantel-Haenszel odds ratio=2.42, P=4.16×10(-7)) at a Bonferroni-corrected level (<1.62×10(-7)). Using two computational algorithms, four copy-number variants (CNVs) were identified in multiple cases that were absent in study controls and markedly less frequent in ∼1500 population-based controls. Of these four constitutional CNVs identified in blood-derived DNA, a 40 kb heterozygous deletion in Chr18q22.1 corresponded with a region frequently showing loss of heterozygosity (LOH) in ileal carcinoid tumor cells based on our meta-analysis of previously published cytogenetic studies (69.7% LOH, 95% confidence interval=60.0-77.9%). We analyzed the constitutional 40 kb deletion on chr18 in our study samples with a real-time quantitative PCR assay; 14/226 cases (6.19%) and 2/97 controls (2.06%) carried the CNV, although the exact boundaries of each deletion have not been determined. Given the small sample size, our findings warrant an independent cohort for a replication study. Owing to the rarity of this disease, we believe these results will provide a valuable resource for future work on this serious condition by allowing others to make efficient use of their samples in targeted studies.

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Published In

Endocr Relat Cancer

DOI

EISSN

1479-6821

Publication Date

February 2011

Volume

18

Issue

1

Start / End Page

171 / 180

Location

England

Related Subject Headings

  • Review Literature as Topic
  • Polymorphism, Single Nucleotide
  • Pilot Projects
  • Oncology & Carcinogenesis
  • Neuroendocrine Tumors
  • Neoplasm Staging
  • Microarray Analysis
  • Meta-Analysis as Topic
  • Male
  • Ileal Neoplasms
 

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Walsh, K. M., Choi, M., Oberg, K., Kulke, M. H., Yao, J. C., Wu, C., … Hoh, J. (2011). A pilot genome-wide association study shows genomic variants enriched in the non-tumor cells of patients with well-differentiated neuroendocrine tumors of the ileum. Endocr Relat Cancer, 18(1), 171–180. https://doi.org/10.1677/ERC-10-0248
Walsh, Kyle M., Murim Choi, Kjell Oberg, Matthew H. Kulke, James C. Yao, Chengqing Wu, Magdalena Jurkiewicz, et al. “A pilot genome-wide association study shows genomic variants enriched in the non-tumor cells of patients with well-differentiated neuroendocrine tumors of the ileum.Endocr Relat Cancer 18, no. 1 (February 2011): 171–80. https://doi.org/10.1677/ERC-10-0248.
Walsh, Kyle M., et al. “A pilot genome-wide association study shows genomic variants enriched in the non-tumor cells of patients with well-differentiated neuroendocrine tumors of the ileum.Endocr Relat Cancer, vol. 18, no. 1, Feb. 2011, pp. 171–80. Pubmed, doi:10.1677/ERC-10-0248.
Walsh KM, Choi M, Oberg K, Kulke MH, Yao JC, Wu C, Jurkiewicz M, Hsu L-I, Hooshmand SM, Hassan M, Janson ET, Cunningham JL, Vosburgh E, Sackler RS, Lifton RP, Dewan AT, Hoh J. A pilot genome-wide association study shows genomic variants enriched in the non-tumor cells of patients with well-differentiated neuroendocrine tumors of the ileum. Endocr Relat Cancer. 2011 Feb;18(1):171–180.
Journal cover image

Published In

Endocr Relat Cancer

DOI

EISSN

1479-6821

Publication Date

February 2011

Volume

18

Issue

1

Start / End Page

171 / 180

Location

England

Related Subject Headings

  • Review Literature as Topic
  • Polymorphism, Single Nucleotide
  • Pilot Projects
  • Oncology & Carcinogenesis
  • Neuroendocrine Tumors
  • Neoplasm Staging
  • Microarray Analysis
  • Meta-Analysis as Topic
  • Male
  • Ileal Neoplasms