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Abstract

Grant Number:	5R01CA066032-09
Project Title:	Melanoma Pathogenesis

PI Information:	Name	Email	Title
	TITUS-ERNSTOFF, LINDA	linda.titus-ernstoff@dartmouth.edu	ASSOCIATE PROFESSOR

Abstract: DESCRIPTION (provided by applicant): We propose a study of melanoma pathogenesis involving two parallel and mutually informative primary aims. First, we will follow melanoma cases (who were previously enrolled in our case-control study) for a second primary melanoma. Virtually all previous studies of multiple primary melanoma were based on clinical or registry databases, which lack follow-up of the cohort at risk. Thus, the rates and risks of this disease remain essentially unknown. Second, we will characterize chromosome 9p21 alterations in a progressive spectrum of melanocytic lesions pertinent to melanoma pathogenesis (benign nevi, atypical nevi, and melanoma). Chromosome 9p21 contains the tumor suppressor gene p16, and our pilot studies indicate that alterations of this region precede the development of morphologic atypia. We will investigate 9p21 alterations (chromosome 9p21 LOH, p16 deletion, and p16 methylation) using lesions already obtained through the parent study, and new lesions obtained through the proposed follow-up effort. We hypothesize that chromosome 9p21 alterations characterize a variant melanoma pathogenesis involving atypical nevi, superficial spreading melanoma, and high risk for multiple primary melanomas. Thus, we will examine chromosome 9p21 alterations in relation to atypical nevi, melanoma histologic subtype, and risk of multiple primary melanoma. We will also examine atypical nevi and superficial spreading melanoma in relation to risk of multiple primary melanoma. Finally, we will explore traditional epidemiologic risk factors in relation to chromosome 9p21 alterations and in relation to risk of multiple primary melanoma. This innovative and costeffective proposal benefits substantially from the work accomplished in our recently completed case-control study, including the prior collection of interview data, the dermatologist-conducted skin examination, the pathology review of all melanocytic lesions, the retrieval and sampling (i.e., slide preparation) of pathology specimens, and the refinement of laboratory techniques for analyzing chromosome 9p21 alterations.

Public Health Relevance:
This Public Health Relevance is not available.

Thesaurus Terms:
cancer risk, melanoma, neoplasm /cancer epidemiology, nevus, pathologic process
cancer prevention, chromosome, longitudinal human study, pigmentation, preneoplastic state, skin disorder diagnosis, solar radiation, tumor suppressor gene
clinical research, histology, human subject, interview, polymerase chain reaction, questionnaire

Institution:	DARTMOUTH COLLEGE
	Office of Sponsored Projects
	HANOVER, NH 03755
Fiscal Year:	2006
Department:	COMMUNITY AND FAMILY MEDICINE
Project Start:	01-APR-1996
Project End:	31-MAR-2009
ICD:	NATIONAL CANCER INSTITUTE
IRG:	EDC

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