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High resolution loss of heterozygosity mapping of 17p13 in thyroid cancer: Hurthle cell carcinomas exhibit a small 411-kilobase common region of allelic imbalance, probably containing a novel tumor suppressor gene.

Abstract
There is strong evidence in many tumor types, including thyroid cancer, for a novel tumor suppressor gene (TSG) at 17p13. To identify the putative thyroid 17p13 TSG we mapped thyroid tumor loss of heterozygosity (LOH) at high resolution within this region. We examined 20 typical follicular thyroid carcinomas (FTC), 19 Hurthle cell carcinomas (HCC), 15 papillary thyroid carcinomas (PTC), and 7 follicular adenomas (FA) for LOH at 17p13 using 18 probes. Complete clinical follow-up data were available for all patients. We confirmed a high 17p13 LOH rate in FTC (18 of 20) and HCC (13 of 19) and showed an association between 17p13 LOH and advanced tumor grade. Only 4 of 15 PTC and 1 of 7 FA displayed 17p13 LOH. In the HCC we identified a narrow minimal common deleted region between D17S1308 (285 kb from the p-telomer) and D17S695 (696 kb from the p-telomer). This region was flanked centromerically by a breakpoint cluster, further suggesting nonrandom deletion. All but 1 of the PTC and FA with 17p LOH and 50% of the affected FTC also showed LOH in this region. These data suggest that a TSG, involved in HCC pathogenesis, is contained within the D17S1308-D17S695 interval. There are several potential candidate TSGs in this region that are worthy of further study.
AuthorsKathryn Farrand, Brett Delahunt, Xiao-Li Wang, Bryan McIver, Ian D Hay, John R Goellner, Norman L Eberhardt, Stefan K G Grebe
JournalThe Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 87 Issue 10 Pg. 4715-21 (Oct 2002) ISSN: 0021-972X [Print] United States
PMID12364463 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • RNA, Messenger
Topics
  • Adenocarcinoma, Follicular (genetics, pathology)
  • Adenoma, Oxyphilic (genetics, pathology)
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Papillary (genetics, pathology)
  • Chromosome Mapping
  • Chromosomes, Human, Pair 17
  • Female
  • Gene Deletion
  • Genes, Tumor Suppressor
  • Humans
  • Loss of Heterozygosity
  • Male
  • Microsatellite Repeats
  • Middle Aged
  • Polymerase Chain Reaction
  • RNA, Messenger (analysis)
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thyroid Neoplasms (genetics, pathology)

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