@article{1051482ad4964314a8d728c0798444bd,
title = "Melanoma cases demonstrate increased carrier frequency of phenylketonuria/hyperphenylalanemia mutations",
abstract = "Identifying novel melanoma genetic risk factors informs screening and prevention efforts. Mutations in the phenylalanine hydroxylase gene (the causative gene in phenylketonuria) lead to reduced pigmentation in untreated phenylketonuria patients, and reduced pigmentation is associated with greater melanoma risk. Therefore, we sought to characterize the relationship between phenylketonuria carrier status and melanoma risk. Using National Newborn Screening Reports, we determined the United States phenylketonuria/hyperphenylalanemia carrier frequency in Caucasians to be 1.76%. We examined three publically available melanoma datasets for germline mutations in the phenylalanine hydroxylase gene associated with classic phenylketonuria and/or hyperphenylalanemia. Mutations were identified in 29/814 melanoma patients, with a carrier frequency of 3.56%. There was a twofold enrichment (p-value = 3.4 × 10−5) compared to the Caucasian frequency of hyperphenylalanemia/phenylketonuria carriers. These data demonstrate a novel association between phenylalanine hydroxylase carrier status and melanoma risk. Further, functional investigation is warranted to determine the link between phenylalanine hydroxylase mutations and melanomagenesis.",
author = "Joshua Arbesman and Sairekha Ravichandran and Pauline Funchain and Thompson, {Cheryl L.}",
note = "Funding Information: Funding for this project was provided by the National Institutes of Health (K12 CA076917 Clinical Oncology Research Career Development Program to J.A.), Dermatology Foundation (Medical Career Development Award to J.A.), and the Fowler Family Foundation (to J.A., C.L.T.). The authors wish to thank the contributors of the phs000178.v9.p8, phs000452.v2.p1, and phs000933.v1.p1 datasets to dbGaP. phs000452.v2.p1: This work was supported by the National Human Genome Research Institute (NHGRI) Large Scale Sequencing Program, Grant U54 HG003067 to the Broad Institute (PI, Lander). phs000178.v9.p8: The results published here are in whole or part based upon data generated by The Cancer Genome Atlas managed by the NCI and NHGRI. Information about TCGA can be found at http://cancergenome. nih.gov./ phs000933.v1.p1: This work was supported by the Yale SPORE in Skin Cancer funded by the National Cancer Institute, grant number 1 P50 CA121974 (R. Halaban, PI), the Melanoma Research Alliance (a Team award to RH, M. Bosenberg, M. Krauthammer and D. F. Stern), Gilead Sciences, Inc. (YS, and RH), the Howard Hughes Medical Institute (R. Lo), the Department of Dermatology, and the Yale Comprehensive Cancer Center. We Publisher Copyright: {\textcopyright} 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd",
year = "2018",
month = jul,
doi = "10.1111/pcmr.12695",
language = "English (US)",
volume = "31",
pages = "529--533",
journal = "Pigment Cell and Melanoma Research",
issn = "1755-1471",
publisher = "Wiley-Blackwell",
number = "4",
}