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Grant Details

Grant Number: 7R01CA231264-05 Interpret this number
Primary Investigator: Asgari, Maryam
Organization: University Of Colorado Denver
Project Title: Pq3 Cutaneous Squamous Cell Carcinoma: Integrating Germline and Somatic Alterations That Underlie Tumor Progression
Fiscal Year: 2023


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. 


Genetically Predicted Serum Vitamin C Levels and Cutaneous Squamous Cell Carcinoma Risk.
Authors: Kim Y. , Yin J. , Le Breton S. , Jorgenson E. , Huang H. , Choquet H. , Asgari M.M. .
Source: The Journal of investigative dermatology, 2023 Apr; 143(4), p. 664-667.
EPub date: 2022-11-05.
PMID: 36343677
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Response to "Comments on sirolimus use and risk of cutaneous squamous cell carcinoma (SCC) in solid organ transplant recipients" (SOTRs).
Authors: Asgari M.M. , Arron S. , Warton E.M. , Quesenberry C.P. , Weisshaar D. .
Source: Journal of the American Academy of Dermatology, 2022 May; 86(5), p. e205-e206.
PMID: 35430053
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Genome-wide association study of actinic keratosis identifies new susceptibility loci implicated in pigmentation and immune regulation pathways.
Authors: Kim Y. , Yin J. , Huang H. , Jorgenson E. , Choquet H. , Asgari M.M. .
Source: Communications biology, 2022-04-21; 5(1), p. 386.
EPub date: 2022-04-21.
PMID: 35449187
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Consensus-Based Recommendations on the Prevention of Squamous Cell Carcinoma in Solid Organ Transplant Recipients: A Delphi Consensus Statement.
Authors: Massey P.R. , Schmults C.D. , Li S.J. , Arron S.T. , Asgari M.M. , Bouwes Bavinck J.N. , Billingsley E. , Blalock T.W. , Blasdale K. , Carroll B.T. , et al. .
Source: JAMA dermatology, 2021-10-01; 157(10), p. 1219-1226.
PMID: 34468690
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Epigenetic Alterations in Keratinocyte Carcinoma.
Authors: Yao Q. , Epstein C.B. , Banskota S. , Issner R. , Kim Y. , Bernstein B.E. , Pinello L. , Asgari M.M. .
Source: The Journal of investigative dermatology, 2021 May; 141(5), p. 1207-1218.
EPub date: 2020-11-16.
PMID: 33212152
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Genetic ancestry, skin pigmentation, and the risk of cutaneous squamous cell carcinoma in Hispanic/Latino and non-Hispanic white populations.
Authors: Jorgenson E. , Choquet H. , Yin J. , Hoffmann T.J. , Banda Y. , Kvale M.N. , Risch N. , Schaefer C. , Asgari M.M. .
Source: Communications biology, 2020-12-14; 3(1), p. 765.
EPub date: 2020-12-14.
PMID: 33318654
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Risk of keratinocyte carcinoma among patients with hidradenitis suppurativa.
Authors: Ashrafzadeh S. , Kim Y. , Peters G.A. , Lee H. , Asgari M.M. .
Source: The British journal of dermatology, 2020 Nov; 183(5), p. 962-964.
EPub date: 2020-07-09.
PMID: 32473027
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Developing a risk prediction model for keratinocyte carcinoma in patients with actinic keratosis.
Authors: Kim Y. , Jorgenson E. , Asgari M.M. .
Source: The British journal of dermatology, 2020 Sep; 183(3), p. 415-416.
EPub date: 2020-05-10.
PMID: 32390191
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Genetic and environmental factors underlying keratinocyte carcinoma risk.
Authors: Choquet H. , Ashrafzadeh S. , Kim Y. , Asgari M.M. , Jorgenson E. .
Source: JCI insight, 2020-05-21; 5(10), .
EPub date: 2020-05-21.
PMID: 32434987
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Association between Human Leukocyte Antigen Type and Keratinocyte Carcinoma Risk in Renal Transplant Recipients.
Authors: Kim Y. , Wojciechowski D. , Pattanayak V. , Lee H. , Asgari M.M. .
Source: The Journal of investigative dermatology, 2020 May; 140(5), p. 995-1002.
EPub date: 2019-10-24.
PMID: 31669059
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