Journal article

Whole exome sequencing identifies a recurrent RQCD1 P131L mutation in cutaneous melanoma

SQ Wong, A Behren, VJ Mar, K Woods, J Li, C Martin, KE Sheppard, R Wolfe, J Kelly, J Cebon, A Dobrovic, GA McArthur

Oncotarget | Impact Journals, LLC | Published : 2015

Abstract

Melanoma is often caused by mutations due to exposure to ultraviolet radiation. This study reports a recurrent somatic C > T change causing a P131L mutation in the RQCD1 (Required for Cell Differentiation1 Homolog) gene identified through whole exome sequencing of 20 metastatic melanomas. Screening in 715 additional primary melanomas revealed a prevalence of ~4%. This represents the first reported recurrent mutation in a member of the CCR4-NOT complex in cancer. Compared to tumors without the mutation, the P131L mutant positive tumors were associated with increased thickness (p = 0.02), head and neck (p = 0.009) and upper limb (p = 0.03) location, lentigo maligna melanoma subtype (p = 0.02) ..

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Grants

Awarded by Victorian Government through the Victorian Cancer Agency Translational Research Program Grant


Awarded by National Health and Medical Research Council of Australia (NHMRC)


Awarded by NHMRC


Funding Acknowledgements

This project was enabled by the Melbourne Melanoma Project funded by the Victorian Government through the Victorian Cancer Agency Translational Research Program Grant (EOI09/27). The authors thank the contributions from staff at the Victorian Cancer Biobank for the collection of blood samples. GM is supported by grants from National Health and Medical Research Council of Australia (NHMRC), #1053792, #1002698, #1053792, #1042980, #1042986 and Practitioner Fellowship 1002654. KS is supported by NHMRC grant # 1042986. The authors wish to acknowledge the Victorian State Government Operational Infrastructure Support Program for partial funding of this project. AB is supported by a Cure Cancer Australia Foundation Fellowship and JC and AB are supported by a grant from the Melanoma Research Alliance (MRA). The authors wish to acknowledge Sonia Mailer, Sue Sturrock, Karen Scott, Aleksandra Logan, Anne Fennessy and Joanne Hawking for their assistance with data and specimen collection. The results shown here are in whole or part based upon data generated by the TCGA Research Network: http://cancergenome.nih.gov/.