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Grant Details

Grant Number: 5P01CA206980-04 Interpret this number
Primary Investigator: Berwick, Marianne
Organization: University Of New Mexico Health Scis Ctr
Project Title: Integration of Clinical and Molecular Biomarkers for Melanoma Survival
Fiscal Year: 2020
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Abstract

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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Publications

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 Jul; 183(1), p. 163-165.
EPub date: 2020-02-19.
PMID: 31958143
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Functional analysis of RPS27 mutations and expression in melanoma.
Authors: Floristán A. , Morales L. , Hanniford D. , Martinez C. , Castellano-Sanz E. , Dolgalev I. , Ulloa-Morales A. , Vega-Saenz de Miera E. , Moran U. , Darvishian F. , et al. .
Source: Pigment cell & melanoma research, 2020 05; 33(3), p. 466-479.
EPub date: 2019-11-22.
PMID: 31663663
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A risk prediction model for the 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, 2020 May; 182(5), p. 1148-1157.
EPub date: 2019-11-27.
PMID: 31520533
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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, 2020 Apr; 140(4), p. 918-922.e7.
EPub date: 2019-09-27.
PMID: 31568773
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Impact of concomitant medication use and immune-related adverse events on response to immune checkpoint inhibitors.
Authors: Gandhi S. , Pandey M. , Ammannagari N. , Wang C. , Bucsek M.J. , Hamad L. , Repasky E. , Ernstoff M.S. .
Source: Immunotherapy, 2020 02; 12(2), p. 141-149.
EPub date: 2020-02-17.
PMID: 32064978
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Epigenetic Silencing of CDR1as Drives IGF2BP3-Mediated Melanoma Invasion and Metastasis.
Authors: Hanniford D. , Ulloa-Morales A. , Karz A. , Berzoti-Coelho M.G. , Moubarak R.S. , Sánchez-Sendra B. , Kloetgen A. , Davalos V. , Imig J. , Wu P. , et al. .
Source: Cancer cell, 2020-01-13; 37(1), p. 55-70.e15.
PMID: 31935372
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The dysfunction of BP180/collagen XVII in keratinocytes promotes melanoma progression.
Authors: Hwang B.J. , Zhang Y. , Brozowski J.M. , Liu Z. , Burette S. , Lough K. , Smith C.C. , Shan Y. , Chen J. , Li N. , et al. .
Source: Oncogene, 2019 12; 38(50), p. 7491-7503.
EPub date: 2019-08-21.
PMID: 31435021
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SNP eQTL status and eQTL density in the adjacent region of the SNP are associated with its statistical significance in GWA studies.
Authors: Gorlov I. , Xiao X. , Mayes M. , Gorlova O. , Amos C. .
Source: BMC genetics, 2019-11-12; 20(1), p. 85.
EPub date: 2019-11-12.
PMID: 31718536
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MC1R Variation in a New Mexico Population.
Authors: White K.A.M. , Dailey Y.T. , Guest D.D. , Zielaskowski K. , Robers E. , Sussman A. , Hunley K. , Hughes C.R. , Schwartz M.R. , Kaphingst K.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, 2019 11; 28(11), p. 1853-1856.
EPub date: 2019-09-05.
PMID: 31488411
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Immune-Checkpoint Protein VISTA Regulates Antitumor Immunity by Controlling Myeloid Cell-Mediated Inflammation and Immunosuppression.
Authors: Xu W. , Dong J. , Zheng Y. , Zhou J. , Yuan Y. , Ta H.M. , Miller H.E. , Olson M. , Rajasekaran K. , Ernstoff M.S. , et al. .
Source: Cancer immunology research, 2019 09; 7(9), p. 1497-1510.
EPub date: 2019-07-24.
PMID: 31340983
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Relationship of Chromosome Arm 10q Variants to Occurrence of Multiple Primary Melanoma in the Population-Based Genes, Environment, and Melanoma (GEM) 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. .
Source: The Journal of investigative dermatology, 2019 06; 139(6), p. 1410-1412.
EPub date: 2018-12-17.
PMID: 30571972
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Identification of a Robust Methylation Classifier for Cutaneous Melanoma Diagnosis.
Authors: Conway K. , Edmiston S.N. , Parker J.S. , Kuan P.F. , Tsai Y.H. , Groben P.A. , Zedek D.C. , Scott G.A. , Parrish E.A. , Hao H. , et al. .
Source: The Journal of investigative dermatology, 2019 06; 139(6), p. 1349-1361.
EPub date: 2018-12-06.
PMID: 30529013
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MC1R variants in childhood and adolescent melanoma: a retrospective pooled analysis of a multicentre cohort.
Authors: Pellegrini C. , Botta F. , Massi D. , Martorelli C. , Facchetti F. , Gandini S. , Maisonneuve P. , Avril M.F. , Demenais F. , Bressac-de Paillerets B. , et al. .
Source: The Lancet. Child & adolescent health, 2019 05; 3(5), p. 332-342.
EPub date: 2019-03-12.
PMID: 30872112
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Utility of TERT Promoter Mutations for Cutaneous Primary Melanoma Diagnosis.
Authors: Thomas N.E. , Edmiston S.N. , Tsai Y.S. , Parker J.S. , Googe P.B. , Busam K.J. , Scott G.A. , Zedek D.C. , Parrish E.A. , Hao H. , et al. .
Source: The American Journal of dermatopathology, 2019 Apr; 41(4), p. 264-272.
PMID: 30211730
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Untouchable genes in the human genome: Identifying ideal targets for cancer treatment.
Authors: Gorlov I.P. , Gorlova O.Y. , Amos C.I. .
Source: Cancer genetics, 2019 02; 231-232, p. 67-79.
EPub date: 2019-01-24.
PMID: 30803560
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A Leukocyte Infiltration Score Defined by a Gene Signature Predicts Melanoma Patient Prognosis.
Authors: Zhao Y. , Schaafsma E. , Gorlov I.P. , Hernando E. , Thomas N.E. , Shen R. , Turk M.J. , Berwick M. , Amos C.I. , Cheng C. .
Source: Molecular cancer research : MCR, 2019 01; 17(1), p. 109-119.
EPub date: 2018-08-31.
PMID: 30171176
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Gene characteristics predicting missense, nonsense and frameshift mutations in tumor samples.
Authors: Gorlov I.P. , Pikielny C.W. , Frost H.R. , Her S.C. , Cole M.D. , Strohbehn S.D. , Wallace-Bradley D. , Kimmel M. , Gorlova O.Y. , Amos C.I. .
Source: BMC bioinformatics, 2018-11-19; 19(1), p. 430.
EPub date: 2018-11-19.
PMID: 30453881
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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 11; 138(11), p. 2398-2404.
EPub date: 2018-05-09.
PMID: 29753029
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Identification of gene expression levels in primary melanoma associated with clinically meaningful characteristics.
Authors: Gorlov I. , Orlow I. , Ringelberg C. , Hernando E. , Ernstoff M.S. , Cheng C. , Her S. , Parker J.S. , Thompson C.L. , Gerstenblith M.R. , et al. .
Source: Melanoma research, 2018 10; 28(5), p. 380-389.
PMID: 29975213
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