Program Project Abstract/Summary
We have brought together 12 institutions in order to promote a better understanding of the biology of
melanoma and how that affects an individual?s survival. Our hypothesis is that primary melanomas will have
molecular and clinical features that will allow the stratification of melanoma tumors at AJCC TNM Stages
IIA/IIB/IIC/IIIA/IIIB, where there is little effective adjuvant therapy, into those with a good prognosis and those
with poor prognosis. The current mortality rate for individuals diagnosed at these stages ranges between 18-
47% for Stages IIA/IIB/IIC and 32-78% for Stage IIIA/IIIB patients. The ability to improve clinical care and
patient outcomes for these patients might be achieved by focusing on the identification and prioritization of
biomarkers ? both molecular and clinical ? that might triage high risk patients for new adjuvant therapies.
In this study, we will identify somatic tumor mutations, CNVs, an immune profile, methylation profiles, and
microRNA/mRNA signatures in primary melanoma that are associated with prognosis, with the ultimate intent
of translating this information into the clinic to personalize care. Currently, there is a dearth of studies in the
melanoma field looking at epidemiologic/genomic factors and melanoma survival. In order to identify, confirm
and develop such biomarkers, we have brought together 9 cohorts of melanoma patients at AJCC TNM stages
IIA/IIB/IIC/IIIA/IIIB, comprising 1000 individuals, 500 of whom have died from their disease as of 2012 and 500
whom have lived at least 5 years. Patients will be frequency matched for stage. As we integrate data from
multiple platforms, we will randomly divide the dataset into a training set (660 tumors, half aggressive and half
non-aggressive) and a validation set (340 tumors, half aggressive and half non-aggressive). Significant
findings in the training set will be replicated in the validation set. These patients have all been treated using
standard-of-care surgery. All patients in this study will have adequate tumor tissue, germline DNA and clinical,
pathologic and demographic information recorded.
Our objective is to identify prognostic biomarkers associated with survival. The goal is to identify patients for
whom more aggressive therapy prior to developing metastases would be relevant, that is would make a
difference to their survival. Our central hypothesis is that melanoma prognosis is largely determined early in
tumor development and that DNA and RNA markers, combined with clinicopathologic and protein
characteristics in primary melanoma will add information to outcome prediction beyond the pathologic features
used in AJCC tumor staging. We are taking an integrative approach to take advantage of and organize the
large amount of information generated from each project. Such information will be available to clinicians and
other investigators as soon as possible.
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