PMID: 7682102Mar 1, 1993Paper

Genetic events in tumour initiation and progression in multiple endocrine neoplasia type 2

Genes, Chromosomes & Cancer
L M MulliganB A Ponder

Abstract

Multiple endocrine neoplasia type 2 (MEN 2) is a familial cancer syndrome arising from mutation at a locus or loci in chromosome region 10p11.2-q11.2. The disease is characterized by medullary thyroid carcinoma (MTC) and pheochromocytoma (Pheo). To assess the genetic events in tumour initiation and progression in this disease, we have compiled an allelotype for MTC and Pheo tumours using polymorphic marker loci from each chromosome arm. Using a panel of 58 tumours, we found frequent allele losses on chromosome arms 1p (42%), 3p (30%), 3q (38%), 11p (11%), 13q (10%), 17p (8%), and 22q (29%). Loss of heterozygosity (LOH) for loci on chromosome 10 was detected in a single tumour where one whole chromosome copy was lost. We used a panel of polymorphic markers for each of chromosomes 1, 3, 11, and 17 to define a shortest region of overlap for these regions. The most frequent allele losses were on chromosome 1, spanning the entire short arm of the chromosome but not loci on 1q. LOH on chromosome 3 encompassed a minimal common region of 3q12-qter. The regions of allelic deletion on chromosome 11 (11pter-p13), 17 (17pter-p11.2), and 13 (13q) encompass known tumour suppressor loci (WTI, TP53, RBI) which must therefore be candidates for ...Continue Reading

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