PQ3 Cutaneous squamous cell carcinoma: Integrating germline and somatic alterations that underlie tumor progression

PQ3 皮肤鳞状细胞癌：肿瘤进展背后的种系和体细胞改变的整合

• 批准号: 10836131
• 负责人: MARYAM Mandana ASGARI
• 金额: $ 37.43万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-16 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10836131
• 关键词: Affect; Age; Aging; American; Area; Biology; Cancer Detection; Cell physiology; Clinical; Clinical Data; Collaborations; Communities; DNA Sequence Alteration; DNA Sequence Rearrangement; Data; Development; Diagnosis; Disease; Environmental Exposure; Environmental Risk Factor; Etiology; Event; Evolution; Exposure to; Genes; Genetic; Genetic Polymorphism; Genetic Risk; Genetic Transcription; Genome; Genomic approach; Genomics; Germ-Line Mutation; Head and neck structure; Health Priorities; Healthcare Systems; Homeostasis; Human Papillomavirus; Immunosuppression; Incidence; Joints; Knowledge; Link; Malignant Neoplasms; Modeling; Mutation; Mutation Analysis; Mutation Detection; Neoplasm Metastasis; Oncogenes; Oncogenic; Organ; Outcome; Pathogenesis; Persons; Pigmentation physiologic function; Predisposition; Prevalence; Prevention strategy; Process; Publishing; Reproducibility; Research; Research Personnel; Resources; Risk; Risk Assessment; Risk Factors; Site; Skin Carcinogenesis; Smoking; Smoking History; Somatic Mutation; Specimen; Squamous cell carcinoma; Stratification; Sun Exposure; Technology; The Cancer Genome Atlas; Therapeutic Intervention; Tissues; Treatment Cost; UV Radiation Exposure; Ultraviolet Rays; United States; Validation; Variant; Work; cancer cell; cancer genomics; cancer risk; clinical predictors; clinical risk; cohort; cost; data integration; data portal; diagnostic biomarker; driver mutation; epidemiology study; epigenomics; exome; exome sequencing; genetic epidemiology; genetic risk factor; genome sequencing; genome wide association study; genomic data; improved; innovation; member; molecular targeted therapies; mortality; new therapeutic target; novel; novel diagnostics; predictive tools; prevent; prognostic; public health relevance; repository; risk prediction; risk variant; sex; skin cancer prevention; skin squamous cell carcinoma; sun damage; therapeutic biomarker; transcriptome; transcriptome sequencing; treatment strategy; tumor; tumor heterogeneity; tumor progression; whole genome

ABSTRACT  Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer in the United States,  affecting over a million people annually, and with significant mortality due to metastasis. Despite it prevalence  and high treatment costs, cSCCs are not included in large-­scale cancer genomics efforts aimed at  understanding the genetic changes arising in cancer cells, such as The Cancer Genome Atlas (TCGA) project.  Thus, genomic alterations in cSCC have not been comprehensively characterized, and novel, molecularly-­ targeted treatments have not been developed. This proposal, modeled after TCGA which is co-­led by Dr. Gad  Getz (Co-­I of this application), represents the largest effort of its kind to analyze genomic changes that drive  cSCC progression. This critical data is needed to identify targets for novel treatment and prevention strategies  of cSCC. Our team was the first to publish a genome-­wide association study that identified ten novel germline  loci associated with increased cSCC risk using the large Genetic Epidemiology Research on Aging (GERA)  cohort. The overall scientific objective of this proposal is to identify and integrate novel tumor  mutational data with previously characterized information on host genetic risk factors and clinical risk  factors to better understand how cancer risk alleles contribute to the development of cSCCs capable of  metastasis. We will analyze 290 cSCCs (145 primary cSCCs that progressed to metastasis and 145 non-­ metastatic primary cSCCs) arising in the well-­characterized GERA cohort to provide a comprehensive  landscape of genomic alterations in cSCCs. We propose the following specific aims: 1) characterize the  genome and transciptome of 290 cSCCs with existing germline data using a tiered approach including whole-­ exome, whole-­genome, and RNA sequencing to identify driver mutations, as well as epigenomic changes;; 2)  integrate the somatic mutational analysis with environmental exposure data to understand how environmental  exposures impact cSCCs with distinct somatic mutational profiles;; and 3) develop a clinically meaningful risk  prediction tool for identifying subjects at risk for metastatic cSCCs that combines germline, somatic, and  clinical data. The approach is innovative because it will increase understanding of the joint contribution of the  germline and somatic genomes for cSCC risk and it will create a publicly accessible cSCC genomic data portal  providing a novel resource for the scientific community. The proposed research is significant because it will  integrate germline and somatic genetic data to gain a comprehensive picture of how the genetics of both the  person and the tumor interact to affect cSCC evolution and progression. The comprehensive, integrated  characterization of key genomic changes in one of the most prevalent and costly cancers will support  advances in developing more effective ways to diagnose, treat and prevent cSCCs and potentially squamous  cell carcinoma arising in other organs.

文摘

项目成果

Consensus-Based Recommendations on the Prevention of Squamous Cell Carcinoma in Solid Organ Transplant Recipients: A Delphi Consensus Statement.

• DOI: 10.1001/jamadermatol.2021.3180
• 发表时间: 2021-10-01
• 期刊: JAMA DERMATOLOGY
• 影响因子: 10.9
• 作者: Massey, Paul R.;Schmults, Chrysalyne D.;Li, Sara J.;Arron, Sarah T.;Asgari, Maryam M.;Bouwes Bavinck, Jan Nico;Billingsley, Elizabeth;Blalock, Travis W.;Blasdale, Katie;Carroll, Bryan T.;Carucci, John A.;Chong, Alvin H.;Christensen, Sean R.;Chung, Christina Lee;DeSimone, Jennifer A.;Ducroux, Emilie;Escutia-Munoz, Begona;Ferrandiz-Pulido, Carla;Fox, Matthew C.;Genders, Roel E.;Geusau, Alexandra;Gjersvik, Petter;Hanlon, Allison M.;Olasz Harken, Edit B.;Hofbauer, Guenther F. L.;Hopkins, R. Samuel;Leitenberger, Justin J.;Loss, Manisha J.;Del Marmol, Veronique;Mascaro, Jose M., Jr.;Myers, Sarah A.;Nguyen, Bichchau T.;Oliveira, Walmar R. P.;Otley, Clark C.;Proby, Charlotte M.;Racz, Emoke;Ruiz-Salas, Veronica;Samie, Faramarz H.;Seckin, Deniz;Shah, Syed N.;Shin, Thuzar M.;Shumack, Stephen P.;Soon, Seaver L.;Stasko, Thomas;Zavattaro, Elisa;Zeitouni, Nathalie C.;Zwald, Fiona O'Reilly;Harwood, Catherine A.;Jambusaria-Pahlajani, Anokhi
• 通讯作者: Jambusaria-Pahlajani, Anokhi

Response to "Comments on sirolimus use and risk of cutaneous squamous cell carcinoma (SCC) in solid organ transplant recipients" (SOTRs).

对“关于实体器官移植受者使用西罗莫司和皮肤鳞状细胞癌 (SCC) 风险的评论”(SOTR) 的回应。

• DOI: 10.1016/j.jaad.2016.01.063
• 发表时间: 2022
• 期刊: Journal of the American Academy of Dermatology
• 影响因子: 13.8
• 作者: Asgari,MaryamM;Arron,Sarah;Warton,EMargaret;QuesenberryJr,CharlesP;Weisshaar,Dana
• 通讯作者: Weisshaar,Dana