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Identification of gene expression levels in primary melanoma associated with clinically meaningful characteristics

Gorlov, Ivana; Orlow, Irenec; Ringelberg, Carola; Hernando, Evad; Ernstoff, Marc S.e; Cheng, Chaoa; Her, Stephanieb; Parker, Joel S.f; Thompson, Cheryl L.g; Gerstenblith, Meg R.h; Berwick, Marianneh,*; Amos, Christopheri,*

doi: 10.1097/CMR.0000000000000473

Factors influencing melanoma survival include sex, age, clinical stage, lymph node involvement, as well as Breslow thickness, presence of tumor-infiltrating lymphocytes based on histological analysis of primary melanoma, mitotic rate, and ulceration. Identification of genes whose expression in primary tumors is associated with these key tumor/patient characteristics can shed light on molecular mechanisms of melanoma survival. Here, we show results from a gene expression analysis of formalin-fixed paraffin-embedded primary melanomas with extensive clinical annotation. The Cancer Genome Atlas data on primary melanomas were used for validation of nominally significant associations. We identified five genes that were significantly associated with the presence of tumor-infiltrating lymphocytes in the joint analysis after adjustment for multiple testing: IL1R2, PPL, PLA2G3, RASAL1, and SGK2. We also identified two genes significantly associated with melanoma metastasis to the regional lymph nodes (PIK3CG and IL2RA), and two genes significantly associated with sex (KDM5C and KDM6A). We found that LEF1 was significantly associated with Breslow thickness and CCNA2 and UBE2T with mitosis. RAD50 was the gene most significantly associated with survival, with a higher level of expression associated with worse survival.

aDepartment of Biomedical Data Science, The Geisel School of Medicine, Dartmouth College, Dartmouth-Hitchcock Medical Center, Lebanon

bDepartment of Computer Science, Dartmouth College, Hanover, New Hampshire

cDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center

dDepartment of Pathology, NYU School of Medicine, New York City

eRoswell Park Cancer Institute, Elm & Carlton, Buffalo, New York

fDepartment of Genetics, Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

gSchool of Medicine, Case Western Reserve University, Cleveland, Ohio

hDepartment of Internal Medicine and Dermatology, University of New Mexico, Albuquerque, New Mexico

iDepartment of Medicine, Baylor College of Medicine, Houston, Texas, USA

*Marianne Berwickh and Christopher Amos contributed equally to the writing of this article.

Correspondence to Marianne Berwick, MD, Department of Internal Medicine and Dermatology, MSC10-5550, 1 University of New Mexico, Albuquerque, NM 87131, USA Tel: +1 203 464 4117; fax: +1 505 272 2579; e-mail:

Received February 19, 2018

Accepted May 15, 2018

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