Tumor suppressor loci on mouse chromosomes 9 and 16 are lost at distinct stages of tumorigenesis in a transgenic model of islet cell carcinoma.

作者: Sareh Parangi , Gerhard Christofori , William Dietrich , Eric S. Lander , Douglas Hanahan

DOI:

关键词: Cancer researchBiologyTumor suppressor geneGeneticsChromosome 16Chromosome 9Locus (genetics)Genetically modified mouseLoss of heterozygosityCarcinogenesisIslet

摘要: Techniques that detect loss of genetic heterozygosity (LOH) have helped elucidate genes involved in human cancers. Previously, a genomewide search using simple sequence length polymorphisms to LOH islet cell tumors arising transgenic mouse model multistage tumorigenesis had revealed two candidate tumor suppressor genes, Loh1 and Loh2 , on chromosomes 9 16, respectively. We now analyzed the early stages development this (hyperplastic, angiogenic, angiogenic islets) for involving regions 16. On chromosome 9, hyperplastic islets reveal low rate (<5%) indistinguishable from background; showed 9% rate, whereas final stage an 18% rate. By contrast, was observed much earlier Notably, 29%, comparable seen end-stage (32%). The results show loci are lost preferentially at different tumorigenesis. observation high is suggests locus may contain angiogenesis suppressor; later appearance contribute progression solid tumor. Tumors containing with partial allowed improved localization region ∼3.2 centiMorgans syntenic 3q 15q.

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