Integration of Clinical and Molecular Biomarkers for Melanoma Survival

黑色素瘤生存的临床和分子生物标志物的整合

• 批准号: 10413854
• 负责人: MARIANNE BERWICK
• 金额: $ 59.82万
• 依托单位: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10413854
• 关键词: Aberrant DNA Methylation; Adjuvant Therapy; Affect; Aggressive behavior; American Joint Committee on Cancer; BRAF gene; Bioinformatics; Biological Assay; Biological Markers; Biology; CD3 Antigens; CD8B1 gene; CDKN2A gene; Candidate Disease Gene; Characteristics; Clinic; Clinical; Copy Number Polymorphism; CpG Island Methylator Phenotype; DNA; DNA Markers; DNA Methylation; DNA methylation profiling; Data; Data Set; Development; Diagnosis; Diagnostic Neoplasm Staging; Disease; Drug Targeting; Epidemiology; Event; FOXP3 gene; Frequencies; Gene Expression; Gene Expression Profile; Genes; Genetic Transcription; Genomics; Goals; Heterogeneity; Immune; Individual; Institution; Joints; Literature; Malignant Neoplasms; Messenger RNA; Methods; Methylation; MicroRNAs; Molecular; Mutation; NF1 mutation; Neoplasm Metastasis; Operative Surgical Procedures; Outcome; PTEN gene; Pathologic; Patient-Focused Outcomes; Patients; Predictive Factor; Prior Therapy; Process; Prognosis; Prognostic Marker; Proteins; RNA marker; Reproducibility; Research Personnel; Role; Somatic Mutation; Specimen; Stage at Diagnosis; Staging; Stains; Stratification; Subgroup; TNM; Testing; Time; Tissues; Training; Translating; Triage; Tumor Tissue; Validation; aggressive therapy; base; care outcomes; clinical biomarkers; clinical care; clinical practice; cohort; high risk; improved; mRNA Expression; melanoma; melanoma biomarkers; molecular marker; molecular subtypes; mortality; nano-string; novel; outcome prediction; personalized care; predictive signature; prognostic; prognostic of survival; prognostic signature; programmed cell death ligand 1; programmed cell death protein 1; programs; protein expression; standard of care; survival outcome; survival prediction; targeted sequencing; treatment response; tumor; tumor heterogeneity

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.

项目摘要/摘要

项目成果

Minimally invasive microbiopsy for genetic profiling of melanocytic lesions: A case series.

• DOI: 10.1016/j.jaad.2021.12.018
• 发表时间: 2022-10
• 期刊: JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
• 影响因子: 13.8
• 作者: Jain, Manu;Autuori, Isidora;Everett, Niasia;Harris, Ucalene;Yamada, Miko;Prow, Tarl;Busam, Klaus;Marchetti, Michael A.;Halpern, Allan C.;Orlow, Irene
• 通讯作者: Orlow, Irene

MC1R Variation in a New Mexico Population.

新墨西哥州人口中的 MC1R 变异。

• DOI: 10.1158/1055-9965.epi-19-0378
• 发表时间: 2019
• 期刊: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
• 作者: White,KirstenAM;Dailey,YvonneT;Guest,DoloresD;Zielaskowski,Kate;Robers,Erika;Sussman,Andrew;Hunley,Keith;Hughes,ChristopherR;Schwartz,MatthewR;Kaphingst,KimberlyA;Buller,DavidB;Hay,JenniferL;Berwick,Marianne
• 通讯作者: Berwick,Marianne

SNP characteristics and validation success in genome wide association studies.

• DOI: 10.1007/s00439-021-02407-8
• 发表时间: 2022-03
• 期刊: Human genetics
• 影响因子: 5.3
• 作者: Gorlova OY;Xiao X;Tsavachidis S;Amos CI;Gorlov IP
• 通讯作者: Gorlov IP

Bayesian network-driven clustering analysis with feature selection for high-dimensional multi-modal molecular data.

• DOI: 10.1038/s41598-021-84514-0
• 发表时间: 2021-03-04
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Zhao Y;Chang C;Hannum M;Lee J;Shen R
• 通讯作者: Shen R

Identification of lung cancer drivers by comparison of the observed and the expected numbers of missense and nonsense mutations in individual human genes.

• DOI: 10.18632/oncotarget.28231
• 发表时间: 2022
• 期刊: ONCOTARGET
• 作者: Gorlova, Olga Y;Kimmel, Marek;Tsavachidis, Spiridon;Amos, Christopher I;Gorlov, Ivan P
• 通讯作者: Gorlov, Ivan P