Journal article
Multiomics Profiling Distinguishes Sebaceous Carcinoma from Benign Sebaceous Neoplasms and Provides Insight into the Genetic Evolution of Sebaceous Carcinogenesis
Clinical cancer research, Vol.30(21), pp.4887-4899
11/01/2024
DOI: 10.1158/1078-0432.CCR-24-1327
PMCID: PMC11530307
PMID: 39287419
Abstract
Sebaceous carcinoma is the third most common nonkeratinocyte skin cancer in the United States with 1,000 cases per year. The clinicopathologic features of sebaceous carcinoma and benign sebaceous neoplasms (adenomas, sebaceomas) can overlap, highlighting the need for molecular biomarkers to improve classification. This study describes the genomic and transcriptomic landscape of sebaceous neoplasms in order to understand tumor etiology and biomarkers relevant for diagnosis and treatment.PURPOSESebaceous carcinoma is the third most common nonkeratinocyte skin cancer in the United States with 1,000 cases per year. The clinicopathologic features of sebaceous carcinoma and benign sebaceous neoplasms (adenomas, sebaceomas) can overlap, highlighting the need for molecular biomarkers to improve classification. This study describes the genomic and transcriptomic landscape of sebaceous neoplasms in order to understand tumor etiology and biomarkers relevant for diagnosis and treatment.We performed whole-genome sequencing (WGS) and whole-transcriptome sequencing (WTS) of sebaceous neoplasms from six academic and two federal healthcare facilities in the United States diagnosed between January 1, 1999, and December 31, 2021.EXPERIMENTAL DESIGNWe performed whole-genome sequencing (WGS) and whole-transcriptome sequencing (WTS) of sebaceous neoplasms from six academic and two federal healthcare facilities in the United States diagnosed between January 1, 1999, and December 31, 2021.We evaluated 98 sebaceous neoplasms: 64 tumors (32 adenomas, 2 sebaceomas, 5 atypical sebaceous neoplasms, 25 carcinomas) had sufficient material for WGS, 96 tumors (42 adenomas, 11 sebaceomas, 8 atypical sebaceous neoplasms, 35 carcinomas) had sufficient material for WTS, and 62 tumors (31 adenomas, 2 sebaceomas, 5 atypical sebaceous neoplasms, 24 carcinomas) had sufficient material for combined WGS and WTS. Overall, we found decreased cholesterol biosynthesis and increased TP53 mutations, copy number gains (chromosome 6, 8q, and/or 18), and tumor mutation burden-high (>10 mutations/MB) in carcinomas compared to adenomas. Although diminished compared to adenomas, most carcinomas still had higher cholesterol biosynthesis than nonmalignant skin. Multiomics profiling also supported a precancerous model of tumor evolution with sebaceomas and atypical sebaceous neoplasms being likely intermediate lesions.RESULTSWe evaluated 98 sebaceous neoplasms: 64 tumors (32 adenomas, 2 sebaceomas, 5 atypical sebaceous neoplasms, 25 carcinomas) had sufficient material for WGS, 96 tumors (42 adenomas, 11 sebaceomas, 8 atypical sebaceous neoplasms, 35 carcinomas) had sufficient material for WTS, and 62 tumors (31 adenomas, 2 sebaceomas, 5 atypical sebaceous neoplasms, 24 carcinomas) had sufficient material for combined WGS and WTS. Overall, we found decreased cholesterol biosynthesis and increased TP53 mutations, copy number gains (chromosome 6, 8q, and/or 18), and tumor mutation burden-high (>10 mutations/MB) in carcinomas compared to adenomas. Although diminished compared to adenomas, most carcinomas still had higher cholesterol biosynthesis than nonmalignant skin. Multiomics profiling also supported a precancerous model of tumor evolution with sebaceomas and atypical sebaceous neoplasms being likely intermediate lesions.The study findings highlight key diagnostic biomarkers for sebaceous carcinoma and suggest that immunotherapy and modulation of cholesterol biosynthesis could be effective treatment strategies.CONCLUSIONSThe study findings highlight key diagnostic biomarkers for sebaceous carcinoma and suggest that immunotherapy and modulation of cholesterol biosynthesis could be effective treatment strategies.
Details
- Title: Subtitle
- Multiomics Profiling Distinguishes Sebaceous Carcinoma from Benign Sebaceous Neoplasms and Provides Insight into the Genetic Evolution of Sebaceous Carcinogenesis
- Creators
- Gabriel J Starrett - National Cancer InstituteBrittany C Baikie - National Cancer InstituteBenjamin K Stoff - Emory UniversityHans E Grossniklaus - Emory UniversityInga Van Buren - Dignity HealthElizabeth G Berry - Oregon Health & Science UniversityRoberto A Novoa - Stanford UniversityKerri E Rieger - Stanford UniversityKavita Y Sarin - Stanford UniversityCharles F Lynch - University of IowaMichael C RoyerMary L Piaskowski - National Cancer InstituteIsaac Brownell - National Institute of Arthritis and Musculoskeletal and Skin DiseasesEmily Y Chu - Hospital of the University of PennsylvaniaRama Godse - Pennsylvania HospitalSuephy C Chen - Duke University School of MedicineKelly J Yu - National Cancer InstituteAlisa M Goldstein - National Cancer InstituteEric A Engels - National Cancer InstituteMichael R Sargen - National Institutes of Health
- Resource Type
- Journal article
- Publication Details
- Clinical cancer research, Vol.30(21), pp.4887-4899
- DOI
- 10.1158/1078-0432.CCR-24-1327
- PMID
- 39287419
- PMCID
- PMC11530307
- NLM abbreviation
- Clin Cancer Res
- ISSN
- 1557-3265
- eISSN
- 1557-3265
- Publisher
- AMER ASSOC CANCER RESEARCH
- Grant note
- Division of Cancer Epidemiology and Genetics (DCEG)Intramural Research Program of the Division of Cancer Epidemiology and GeneticsCenter for Cancer Research, National Cancer Institute, National Institutes of Health
This work was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and the Center for Cancer Research, National Cancer Institute, National Institutes of Health (G.J. Starrett, K.J. Yu, A.M. Goldstein, E.A. Engels, M.R. Sargen). We would like to thank the CCR Genomics Core and CCR Sequencing Facility for their assistance with sequencing. This work utilized the computational resources of the NIH HPC Biowulf cluster (http://hpc.nih.gov). We would also like to thank Francisco J. Rentas for assistance with tumor sample acquisition from the Joint Pathology Center, Silver Spring, MD.
- Language
- English
- Electronic publication date
- 09/17/2024
- Date published
- 11/01/2024
- Academic Unit
- Epidemiology
- Record Identifier
- 9984709511402771
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