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This research was funded by The Catalan Society of Endocrinology and Nutrition (Fellowship 2015/2016), Hospital Clinic de Barcelona (End-of-Residence Award 2016/2017), and The Spanish Society of Endocrinology and Nutrition (Beca Morreale-Escobar 2017/2018). We had the collaboration of the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (USA).

Analysis of institutional authors

Mora MAuthorHalperin IAuthorOriola JAuthor

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September 22, 2020
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NOP53 as A Candidate Modifier Locus for Familial Non-Medullary Thyroid Cancer

Publicated to:Genes. 10 (11): E899- - 2019-11-01 10(11), DOI: 10.3390/genes10110899

Authors: Orois A, Gara SK, Mora M, Halperin I, Martínez S, Alfayate R, Kebebew E, Oriola J

Affiliations

Department of Biochemistry and Molecular Genetics, CDB, Hospital Clínic, 08036 Barcelona, Spain. - Author
Department of Endocrinology and Nutrition, Hospital de Elda, 03600 Elda, Alicante, Spain. - Author
Department of Endocrinology and Nutrition, Hospital General Universitario de Alicante, 03010 Alicante, Spain. - Author
Department of Endocrinology and Nutrition, ICMDM, Hospital Clinic, 08036 Barcelona, Spain. - Author
Department of Surgery and Stanford Cancer Institute, Stanford University, Stanford, CA 9430, USA. - Author
Faculty of Medicine, University of Barcelona, 08007 Barcelona, Spain. - Author
Hosp Clin Barcelona, CDB, Dept Biochem & Mol Genet, Barcelona 08036, Spain - Author
Hosp Clin Barcelona, ICMDM, Dept Endocrinol & Nutr, Barcelona 08036, Spain - Author
Hosp Elda, Dept Endocrinol & Nutr, Alicante 03600, Spain - Author
Hosp Gen Univ Alicante, Dept Endocrinol & Nutr, Alicante 03010, Spain - Author
NCI, Thorac Surg Branch, NIH, Bethesda, MD 20892 USA - Author
Stanford Univ, Dept Surg, Stanford, CA 94305 USA - Author
Stanford Univ, Stanford Canc Inst, Stanford, CA 94305 USA - Author
Thoracic Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. - Author
Univ Barcelona, Fac Med, E-08007 Barcelona, Spain - Author
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Abstract

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.

Keywords

Breast-cancerCarcinomaExpressionGenetic abnormalitiesGltscr2GrowthLinkage analysisMolecular testingNop53Oncogenic mutationsPredisposeThyroid cancerVariants

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Genes due to its progression and the good impact it has achieved in recent years, according to the agency Scopus (SJR), it has become a reference in its field. In the year of publication of the work, 2019, it was in position , thus managing to position itself as a Q1 (Primer Cuartil), in the category Genetics.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 3.39, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions Aug 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-08-02, the following number of citations:

  • WoS: 10
  • Europe PMC: 9

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-08-02:

  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 30 (PlumX).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: United States of America.

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: Last Author (Oriola Ambrós, Josep).