Fine-structure deletion mapping of 10q22-24 identifies regions of loss of heterozygosity and suggests that sporadic follicular thyroid adenomas and follicular thyroid carcinomas develop along distinct neoplastic pathways.
Previous studies have demonstrated frequent loss of heterozygosity (LOH) of markers on chromosome arm 10q in both follicular thyroid carcinomas (FTCs) and follicular thyroid adenomas (FAs). A novel tumor suppressor gene, PTEN, has been mapped to 10q23.3 and is the susceptibility gene for Cowden syndrome, an autosomal dominant disorder characterized by multiple hamartomas and a risk of benign and malignant tumors of the breast and thyroid. Studies examining the relationship of somatic PTEN status and follicular thyroid neoplasms have only demonstrated a variable subset of tumors that have somatic monoallelic deletions of PTEN, suggesting that other tumor suppressor genes may be present in this region. We therefore sought to conduct a detailed examination of LOH of 20 polymorphic markers in a 19-cM region spanning 10q22-24, including PTEN, in 44 FAs and 17 FTCs. Using this fine-structure somatic mapping approach, we defined at least two novel regions of LOH in follicular adenomas and follicular carcinomas, suggesting the presence of at least two distinct tumor suppressor genes that may play a role in thyroid neoplasia. Furthermore, the difference in patterns of LOH in adenomas versus carcinomas lends additional support to the hypothesis that adenomas and carcinomas can develop along two separate, nonserial pathways. Genes Chromosomes Cancer 26:322-328, 1999.
Yeh
J J
JJ
Clinical Cancer Genetics and Human Cancer Genetics Programs, Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43210, USA.
Marsh
D J
DJ
Zedenius
J
J
Dwight
T
T
Delbridge
L
L
Robinson
B G
BG
Eng
C
C
D018263:Adenocarcinoma, Follicular / Q000235:genetics*; D000236:Adenoma / Q000235:genetics*; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D004273:DNA, Neoplasm / Q000032:analysis; D005819:Genetic Markers; D006801:Humans; D019656:Loss of Heterozygosity; D013964:Thyroid Neoplasms / Q000235:genetics*
D004273:DNA, Neoplasm; D005819:Genetic Markers