GENE PROBES IN THE FAMMM

Project: Research project

Description

The investigation will involve the study of gene probes in a unique
resource of 70 families with the familial atypical multiple mole
melanoma (FAMMM) syndrome which are in variable stages of
extension and documentation. Utilizing 19 of these kindreds, we
shall select 54 patients with pathologically verified FAMMM
moles, some of whom will have manifested cutaneous malignant
melanoma (CMM), and 116 of their first degree relatives (50% risk
for FAMMM). Utilizing peripheral blood lymphocytes from which
DNA will be obtained, we will perform a linkage study employing
a large number of well characterized genetic markers. This will
include several hundred variable number tandem repeat (VNTR)
markers and the more conventional site polymorphisms, all of
which have been under investigation at Dr. White's laboratories of
the Howard Hughes Medical Institute at the University of Utah
School of Medicine at Salt Lake City. Linkage analysis programs
at the center will be employed for this phase of the study.
Concurrent with this gene probe investigation, we shall capitalize
upon and expand our existing FAMMM resource in order to better
comprehend its genetics and natural history in context with
dysplastic (atypical) nevi and CMM as well as extra-nonmelanotic
forms of cancer. We will study a consecutive series of patients
with dysplastic nevi and/or CMM, and their family members.
Tissues from patients with atypical moles, CMM, and
nonmelanotic cancer will be studied by a cadre of pathologists.
Association among moles, CMM, and nonmelanotic cancer will be
evaluted. These linkage and clinicopathologic studies will enable
us to test hypotheses generated by our group which propose that
this cancer-associated genodermatosis is due to an autosomal
dominantly inherited pleiotropic gene which, in addition to
causing atypical nevi and CMM, also predisposes to a variety of
systemic forms of cancer. The full extent of the tumor spectrum
remains controversial. Our biostatistical analyses will also take
into account and evaluate the frequently neglected problem of
possible etiologic and phenotypic heterogeneity within the
FAMMM. This investigation is exceedingly important in that the
FAMMM appears to be etiologic in a highly significant fraction of
the overall malignant melanoma burden. Controversy exists
relevant to so-called sporadic forms vs. genetic variants of
FAMMM. Because of limitations in identification of the atypical
nevus phenotype from both the clinical and dermatopathological
standpoints, it is crucial that we develop gene probes of
acceptable sensitivity and specificity for genotype. Given the
technology available to us, this may lead to the identification of
the deleterious gene.
StatusFinished
Effective start/end date4/15/8811/30/91

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

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Skin
Genes
Neoplasms
Nevus
Genetic Pleiotropy
Dysplastic Nevus Syndrome
Minisatellite Repeats
Natural History
Genetic Markers
Documentation
Melanoma
Genotype
Medicine
Lymphocytes
Phenotype
Sensitivity and Specificity