Melanoma RAS/BRAF Mutation: Heterogeneity-Risk-Prognosis

黑色素瘤 RAS/BRAF 突变：异质性-风险-预后

• 批准号: 8607510
• 负责人: NANCY E THOMAS
• 金额: $ 47.94万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-13 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8607510
• 关键词: Address; Affect; Age; BRAF gene; Biometry; Breslow Thickness; CX3CL1 gene; Case-Control Studies; Cell Line; Characteristics; Chemokine Receptor Gene; Climate; Collaborations; Complex; Comprehensive Cancer Center; Data; Dermatology; Dermatopathology; Development; Diagnosis; Disease Association; Enrollment; Environment; Environmental Protection; Environmental Risk Factor; Epidemiology; Gene Mutation; Genes; Genetic Polymorphism; Genetic Variation; Genotype; Geographic Locations; Goals; Hair; Heterogeneity; Immunity; Incidence; Individual; Inherited; International; Investigation; Knowledge; Laboratories; Lead; Link; Malignant Neoplasms; Medical; Melanoma Cell; Methods; Minnesota; Modeling; Molecular; Molecular Biology; Molecular Epidemiology; Mutation; Neoplasm Metastasis; Newly Diagnosed; Oncogenic; Outcome; Participant; Pathology; Pathway interactions; Patients; Play; Positioning Attribute; Prevention; Process; Prognostic Marker; Receptor Gene; Research; Research Personnel; Residual state; Resistance; Risk; Risk Factors; Role; Sample Size; Single Nucleotide Polymorphism; Site; Staging; Technology; Testing; The Sun; Translating; Tumor Immunity; Ulcer; Ultraviolet Rays; Variant; Work; aging gene; alpha-Melanocyte stimulating hormone; angiogenesis; base; chemokine; chemokine receptor; epidemiologic data; evidence based guidelines; gene environment interaction; genome wide association study; immunogenicity; improved; innovation; knowledge base; loss of function; melanoma; mortality; outcome forecast; population based; prognostic; programs; public health relevance; receptor; trait; tumor; tumor progression; tumorigenesis; ultraviolet

DESCRIPTION (provided by applicant): Melanoma can metastasize at an early stage, and these metastases are typically resistant to medical treatment. In addition, melanoma is rising in incidence and mortality, greatly increasing the need for methods of prevention and treatment. Evidence suggests that chemokines and their receptors are important regulators of tumor immunity, progression, metastasis, and, angiogenesis in many cancers, including melanoma. The activities of chemokines and their receptors have been shown to be altered by polymorphisms but the impact of these changes on melanoma remains to be elucidated. Preliminary work has identified a polymorphism of a single chemokine receptor that influences the risk of melanoma, but as yet no comprehensive investigations of links between melanoma and chemokine or chemokine receptor polymorphisms have been performed. We propose to detail inherited variations in chemokines and their receptors and determine their associations with melanoma risk, survival, and NRAS and BRAF mutational subtypes in the large international population-based Genes, Environment, and Melanoma (GEM) study. We will also determine whether these relationships are modified by age, ultraviolet exposure, phenotypic traits, and polymorphisms in other genes. Few previous studies have simultaneously addressed the 'immunogenicity' of melanoma along with the oncogenic pathways. The results are likely to improve risk prediction and evidence-based recommendations for environmental protection and enable better outcomes prediction and customization of treatment paradigms for affected patients.

描述（由申请人提供）：黑色素瘤可以在早期阶段转移，并且这些转移通常对药物治疗有抵抗力。此外，黑色素瘤的发病率和死亡率正在上升，大大增加了对预防和治疗方法的需求。有证据表明，趋化因子及其受体是许多癌症（包括黑色素瘤）中肿瘤免疫、进展、转移和血管生成的重要调节因子。趋化因子及其受体的活性已被证明是由多态性改变，但这些变化对黑色素瘤的影响仍有待阐明。初步工作已经确定了一个单一的趋化因子受体的多态性，影响黑色素瘤的风险，但尚未全面调查黑色素瘤和趋化因子或趋化因子受体多态性之间的联系已经进行。我们建议详细说明趋化因子及其受体的遗传变异，并在大型国际人群为基础的基因，环境和黑色素瘤（GEM）研究中确定其与黑色素瘤风险，生存率，NRAS和BRAF突变亚型的相关性。我们还将确定这些关系是否会受到年龄、紫外线暴露、表型性状和其他基因多态性的影响。以前很少有研究同时解决了黑色素瘤的“免疫原性”沿着致癌途径。这些结果可能会改善环境保护的风险预测和循证建议，并为受影响的患者提供更好的结果预测和定制治疗模式。

项目成果

Validation of the VE1 immunostain for the BRAF V600E mutation in melanoma.

• DOI: 10.1111/cup.12364
• 发表时间: 2014-09
• 期刊: Journal of cutaneous pathology
• 影响因子: 1.7
• 作者: Pearlstein MV;Zedek DC;Ollila DW;Treece A;Gulley ML;Groben PA;Thomas NE
• 通讯作者: Thomas NE

No prognostic value added by vitamin D pathway SNPs to current prognostic system for melanoma survival.

• DOI: 10.1371/journal.pone.0174234
• 发表时间: 2017
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Luo L;Orlow I;Kanetsky PA;Thomas NE;Fang S;Lee JE;Berwick M;Lee JH;GEM Study Group
• 通讯作者: GEM Study Group

Appearance Normalization of Histology Slides.

• DOI: 10.1007/978-3-642-15948-0_8
• 发表时间: 2010
• 期刊: LECTURE NOTES IN ARTIFICIAL INTELLIGENCE
• 作者: Niethammer, Marc;Borland, David;Marron, J. S.;Woosley, John;Thomas, Nancy E.
• 通讯作者: Thomas, Nancy E.

DNA methylation profiles in primary cutaneous melanomas are associated with clinically significant pathologic features.

原发性皮肤黑色素瘤中的 DNA 甲基化谱与临床显着的病理特征相关。

• DOI: 10.1111/pcmr.12289
• 发表时间: 2014
• 期刊: Pigment cell & melanoma research
• 影响因子: 4.3
• 作者: Thomas,NancyE;Slater,NathanielA;Edmiston,SharonN;Zhou,Xin;Kuan,Pei-Fen;Groben,PamelaA;Carson,CraigC;Hao,Honglin;Parrish,Eloise;Moschos,StergiosJ;Berwick,Marianne;Ollila,DavidW;Conway,Kathleen
• 通讯作者: Conway,Kathleen

Sun exposure and melanoma survival: a GEM study.

• DOI: 10.1158/1055-9965.epi-14-0431
• 发表时间: 2014-10
• 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: Berwick M;Reiner AS;Paine S;Armstrong BK;Kricker A;Goumas C;Cust AE;Thomas NE;Groben PA;From L;Busam K;Orlow I;Marrett LD;Gallagher RP;Gruber SB;Anton-Culver H;Rosso S;Zanetti R;Kanetsky PA;Dwyer T;Venn A;Lee-Taylor J;Begg CB;GEM Study Group
• 通讯作者: GEM Study Group