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 synd rome, an autosomal dominant disorder characterized by multiple hamartomas a nd a risk of benign and malignant tumors of the breast and thyroid. Studies examining the relationship of somatic PTEN status and follicular thyroid n eoplasms have only demonstrated a variable subset of tumors that have somat ic monoallelic deletions of PTEN, suggesting that other tumor suppressor ge nes may be present in this region. We therefore sought to conduct a detaile d examination of LOH of 20 polymorphic markers in a 19-cM region spanning 1 0q22-24, including PTEN, in 44 FAs and 17 FTCs. Using this fine-structure s omatic mapping approach, we defined at least two novel regions of LOH in fo llicular adenomas and follicular carcinomas, suggesting the presence of at least two distinct tumor suppressor genes that may play a role in thyroid n eoplasia. Furthermore, the difference in patterns of LOH in adenomas versus carcinomas lends additional support to the hypothesis that adenomas and ca rcinomas can develop along two separate, nonserial pathways. (C) 1999 Wiley -Liss, Inc.