Distinct Biological Types of Ocular Adnexal Sebaceous Carcinoma: HPV-Driven and Virus-Negative Tumors Arise through Nonoverlapping Molecular-Genetic Alterations.

Courtney W Hudgens, Bita Esmaeli, Anna Yemelyanova, Victor G Prieto, Kenna Shaw, Agda Karina Eterovic, Ken Chen, Tae-Boom Kim, Doina Ivan, Michael T Tetzlaff, Mark Routbort, Diana Bell, Bo Peng, Thomas L Kandl, Oded Sagiv, Jing Ning, Jonathan L Curry

Journal: Clinical cancer research : an official journal of the American Association for Cancer Research 2020;25(4):1280-1290

PMID: 30420449

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Abstract

PURPOSE

Ocular adnexal (OA) sebaceous carcinoma is an aggressive malignancy of the eyelid and ocular adnexa that frequently recurs and metastasizes, and effective therapies beyond surgical excision are lacking. There remains a critical need to define the molecular-genetic drivers of the disease to understand carcinomagenesis and progression and to devise novel treatment strategies.

EXPERIMENTAL DESIGN

We present next-generation sequencing of a targeted panel of cancer-associated genes in 42 and whole transcriptome RNA sequencing from eight OA sebaceous carcinomas from 29 patients.

RESULTS

We delineate two potentially distinct molecular-genetic subtypes of OA sebaceous carcinoma. The first is defined by somatic mutations impacting and/or [20/29 (70%) patients, including 10 patients whose primary tumors contained coexisting and mutations] with frequent concomitant mutations affecting genes. These tumors arise in older patients and show frequent local recurrence. The second subtype [9/29 (31%) patients] lacks mutations affecting , or family members, but in 44% (4/9) of these tumors, RNA sequencing and hybridization studies confirm transcriptionally active high-risk human papillomavirus. These tumors arise in younger patients and have not shown local recurrence.

CONCLUSIONS

Together, our findings establish a potential molecular-genetic framework by which to understand the development and progression of OA sebaceous carcinoma and provide key molecular-genetic insights to direct the design of novel therapeutic interventions.

Address: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas. [email protected] [email protected].; Department of Translational and Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Orbital Oncology and Ophthalmic Plastic Surgery, Department of Plastic Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Orbital Oncology and Ophthalmic Plastic Surgery, Department of Plastic Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas. [email protected] [email protected].

DOI: 10.1158/1078-0432.CCR-18-1688