NOP53 as A Candidate Modifier Locus for Familial Non-Medullary Thyroid Cancer.
Por:
Orois A, Gara SK, Mora M, Halperin I, Martínez S, Alfayate R, Kebebew E and Oriola J
Publicada:
7 nov 2019
Ahead of Print:
7 nov 2019
Resumen:
Nonsyndromic familial non-medullary thyroid cancer (FNMTC) represents 3-9% of thyroid cancers, but the susceptibility gene(s) remain unknown. We designed this multicenter study to analyze families with nonsyndromic FNMTC and identify candidate susceptibility genes. We performed exome sequencing of DNA from four affected individuals from one kindred, with five cases of nonsyndromic FNMTC. Single Nucleotide Variants, and insertions and deletions that segregated with all the affected members, were analyzed by Sanger sequencing in 44 additional families with FNMTC (37 with two affected members, and seven with three or more affected members), as well as in an independent control group of 100 subjects. We identified the germline variant p. Asp31His in NOP53 gene (rs78530808, MAF 1.8%) present in all affected members in three families with nonsyndromic FNMTC, and not present in unaffected spouses. Our functional studies of NOP53 in thyroid cancer cell lines showed an oncogenic function. Immunohistochemistry exhibited increased NOP53 protein expression in tumor samples from affected family members, compared with normal adjacent thyroid tissue. Given the relatively high frequency of the variant in the general population, these findings suggest that instead of a causative gene, NOP53 is likely a low-penetrant gene implicated in FNMTC, possibly a modifier.
Filiaciones:
Orois A:
Department of Endocrinology and Nutrition, ICMDM, Hospital Clinic, 08036 Barcelona, Spain
Gara SK:
Thoracic Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Mora M:
Department of Endocrinology and Nutrition, ICMDM, Hospital Clinic, 08036 Barcelona, Spain
Faculty of Medicine, University of Barcelona, 08007 Barcelona, Spain
Halperin I:
Department of Endocrinology and Nutrition, ICMDM, Hospital Clinic, 08036 Barcelona, Spain
Faculty of Medicine, University of Barcelona, 08007 Barcelona, Spain
Martínez S:
Department of Endocrinology and Nutrition, Hospital de Elda, 03600 Elda, Alicante, Spain
:
Department of Endocrinology and Nutrition, Hospital General Universitario de Alicante, 03010 Alicante, Spain
Kebebew E:
Department of Surgery and Stanford Cancer Institute, Stanford University, Stanford, CA 9430, USA
Oriola J:
Faculty of Medicine, University of Barcelona, 08007 Barcelona, Spain
Department of Biochemistry and Molecular Genetics, CDB, Hospital Clínic, 08036 Barcelona, Spain
Green Published, gold
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