Grant Number:	1R03CA125829-01 Interpret this number
Primary Investigator:	Orlow, Irene
Organization:	Sloan-Kettering Inst Can Research
Project Title:	Mutational Analysis of Clonality in Multiple Primary Melanoma
Fiscal Year:	2006

DESCRIPTION (provided by applicant): Melanoma patients are very frequently diagnosed with putative second primaries. Indeed, some patients experience multiple occurrences of the disease. While these phenomena could be explained by strong genetic predisposition, it is also possible that a significant subset of these second and higher-order primaries are actually (clonal) recurrences of the initial primary, since many studies in other sites have occasionally confirmed a clonal origin for new tumors that are presumed to be independent on the basis of classical pathological criteria. Accurate classification of subsequent primaries has important clinical implications, but it is also of considerable relevance for epidemiologic research, since patients with multiple primaries are increasingly being recognized as an important resource, especially for studies of rare genetic factors. Our goal in this study is to conduct a pilot clonality investigation in patients diagnosed with double primary melanoma. Specifically, in order to identify molecular differences and similarities between tumors we propose to: (1) compare the mutational profiles of pairs of primary melanomas from individual patients with double malignancies using micro-satellite instability markers; and (2) reproduce the strategy in Aim 1 using array CGH rather than candidate markers. We will test 25 sets of first and second primary lesions from individuals diagnosed with double primary melanoma. This study will be the first to assess evidence for clonality in multiple primary melanoma. Our results will have implications for the pathologic classification of melanoma, clinical decision making for a patient with a second primary, and epidemiologic research methods. If results from this study suggest that cutaneous metastases are frequently diagnosed as second malignancies, then we will plan a subsequent study using the large population-based resource of tumor tissues from patients with double primary melanoma collected from the international population-based GEM Study (CA83180), designed to determine definitively the frequency of mis-diagnosis, and to determine predictors of tumors that would benefit from mutational profiling to validate the diagnosis.




Association of functional, inherited vitamin D-binding protein variants with melanoma-specific death.
Authors: Gibbs D.C. , Thomas N.E. , Kanetsky P.A. , Luo L. , Busam K.J. , Cust A.E. , Anton-Culver H. , Gallagher R.P. , Zanetti R. , Rosso S. , et al. .
Source: Jnci Cancer Spectrum, 2023-08-31 00:00:00.0; 7(5), .
PMID: 37494457
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Sex-Specific Associations of MDM2 and MDM4 Variants with Risk of Multiple Primary Melanomas and Melanoma Survival in Non-Hispanic Whites.
Authors: Ward S.V. , Autuori I. , Luo L. , LaPilla E. , Yoo S. , Sharma A. , Busam K.J. , Olilla D.W. , Dwyer T. , Anton-Culver H. , et al. .
Source: Cancers, 2023-05-11 00:00:00.0; 15(10), .
EPub date: 2023-05-11 00:00:00.0.
PMID: 37345045
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Association of Melanoma-Risk Variants with Primary Melanoma Tumor Prognostic Characteristics and Melanoma-Specific Survival in the GEM Study.
Authors: Davari D.R. , Orlow I. , Kanetsky P.A. , Luo L. , Busam K.J. , Sharma A. , Kricker A. , Cust A.E. , Anton-Culver H. , Gruber S.B. , et al. .
Source: Current Oncology (toronto, Ont.), 2021-11-16 00:00:00.0; 28(6), p. 4756-4771.
EPub date: 2021-11-16 00:00:00.0.
PMID: 34898573
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Disease-Associated Risk Variants in ANRIL are Associated with Tumor-Infiltrating Lymphocytes Presence in Primary Melanomas in the Population-Based GEM Study.
Authors: Davari D.R. , Orlow I. , Kanetsky P.A. , Luo L. , Edmiston S.N. , Conway K. , Parrish E.A. , Hao H. , Busam K.J. , Sharma A. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2021-10-04 00:00:00.0; , .
EPub date: 2021-10-04 00:00:00.0.
PMID: 34607836
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Comparison of community pathologists with expert dermatopathologists evaluating Breslow thickness and histopathologic subtype in a large international population-based study of melanoma.
Authors: Yardman-Frank J.M. , Bronner B. , Rosso S. , From L. , Busam K. , Groben P. , Tucker P. , Cust A. , Armstrong B. , Kricker A. , et al. .
Source: Jaad International, 2021 Sep; 4, p. 25-27.
EPub date: 2021-06-01 00:00:00.0.
PMID: 34409386
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Association of Known Melanoma Risk Factors with Primary Melanoma of the Scalp and Neck.
Authors: Wood R.P. , Heyworth J.S. , McCarthy N.S. , Mauguen A. , Berwick M. , Thomas N.E. , Millward M.J. , Anton-Culver H. , Cust A.E. , Dwyer T. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2020-08-20 00:00:00.0; , .
EPub date: 2020-08-20 00:00:00.0.
PMID: 32856602
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Association of IRF4 single-nucleotide polymorphism rs12203592 with melanoma-specific survival.
Authors: Ward S.V. , Gibbs D.C. , Orlow I. , Thomas N.E. , Kanetsky P.A. , Luo L. , Cust A.E. , Anton-Culver H. , Gruber S.B. , Gallagher R.P. , et al. .
Source: The British Journal Of Dermatology, 2020-01-20 00:00:00.0; , .
EPub date: 2020-01-20 00:00:00.0.
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Inherited Melanoma Risk Variants Associated with Histopathologically Amelanotic Melanoma.
Authors: Gibbs D.C. , Orlow I. , Vernali S. , Powell H.B. , Kanetsky P.A. , Luo L. , Busam K.J. , Sharma A. , Kricker A. , Armstrong B.K. , et al. .
Source: The Journal Of Investigative Dermatology, 2019-09-27 00:00:00.0; , .
EPub date: 2019-09-27 00:00:00.0.
PMID: 31568773
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A risk prediction model for development of subsequent primary melanoma in a population-based cohort.
Authors: Cust A.E. , Badcock C. , Smith J. , Thomas N.E. , Haydu L.E. , Armstrong B.K. , Law M.H. , Thompson J.F. , Kanetsky P.A. , Begg C.B. , et al. .
Source: The British Journal Of Dermatology, 2019-09-14 00:00:00.0; , .
EPub date: 2019-09-14 00:00:00.0.
PMID: 31520533
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Relationship of Chromosome Arm 10q Variants to Occurrence of Multiple Primary Melanoma in the Population-Based Genes, Environment, and Melanoma Study.
Authors: Miles J.A. , Orlow I. , Kanetsky P.A. , Luo L. , Cust A.E. , Armstrong B.K. , Kricker A. , Anton-Culver H. , Gruber S.B. , Gallagher R.P. , et al. .
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EPub date: 2018-12-17 00:00:00.0.
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Inherited Genetic Variants Associated with Melanoma BRAF/NRAS Subtypes.
Authors: Thomas N.E. , Edmiston S.N. , Orlow I. , Kanetsky P.A. , Luo L. , Gibbs D.C. , Parrish E.A. , Hao H. , Busam K.J. , Armstrong B.K. , et al. .
Source: The Journal Of Investigative Dermatology, 2018-05-09 00:00:00.0; , .
EPub date: 2018-05-09 00:00:00.0.
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A metastasis or a second independent cancer? Evaluating the clonal origin of tumors using array copy number data.
Authors: Ostrovnaya I. , Olshen A.B. , Seshan V.E. , Orlow I. , Albertson D.G. , Begg C.B. .
Source: Statistics In Medicine, 2010-07-10 00:00:00.0; 29(15), p. 1608-21.
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Evaluation of the clonal origin of multiple primary melanomas using molecular profiling.
Authors: Orlow I. , Tommasi D.V. , Bloom B. , Ostrovnaya I. , Cotignola J. , Mujumdar U. , Busam K.J. , Jungbluth A.A. , Scolyer R.A. , Thompson J.F. , et al. .
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