Oncotarget

Research Papers:

Large deletion at the CDC73 gene locus and search for predictive markers of the presence of a CDC73 genetic lesion

Lucia Anna Muscarella, Daniela Turchetti, Andrea Fontana, Filomena Baorda, Orazio Palumbo, Annamaria la Torre, Danilo de Martino, Renato Franco, Nunzia Simona Losito, Andrea Repaci, Uberto Pagotto, Luigia Cinque, Massimiliano Copetti, Maria Grazia Chiofalo, Luciano Pezzullo, Paolo Graziano, Alfredo Scillitani and Vito Guarnieri _

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Oncotarget. 2018; 9:20721-20733. https://doi.org/10.18632/oncotarget.25067

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Abstract

Lucia Anna Muscarella1,*, Daniela Turchetti2,*, Andrea Fontana3,*, Filomena Baorda4, Orazio Palumbo4, Annamaria la Torre1,5, Danilo de Martino6, Renato Franco7, Nunzia Simona Losito7, Andrea Repaci8, Uberto Pagotto8, Luigia Cinque4, Massimiliano Copetti3, Maria Grazia Chiofalo9, Luciano Pezzullo9, Paolo Graziano10, Alfredo Scillitani11 and Vito Guarnieri4

1Laboratory of Oncology, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo 71013, Italy

2Medical Genetics, Sant’Orsola Malpighi Hospital, University of Bologna, Bologna 40138, Italy

3Unit of Biostatistics, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo 71013, Italy

4Medical Genetics, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo 71013, Italy

5ISBReMIT, Institute for Stem-cell Biology, Regenerative Medicine and Innovative Therapies, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo 71013, Italy

6Thoracic Surgery, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo 71013, Italy

7Pathology , Istituto Nazionale Tumori, Fondazione “G. Pascale”, Napoli 80131, Italy

8Endocrinology, Sant’Orsola Malpighi Hospital, University of Bologna, Bologna 40138, Italy

9Thyroid and Parathyroid Surgery Unit, Istituto Nazionale Tumori, Fondazione “G. Pascale”, Napoli 80131, Italy

10Pathology, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo 71013, Italy

11Endocrinology, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo 71013, Italy

*These authors contributed equally to this work

Correspondence to:

Vito Guarnieri, email: v.guarnieri@operapadrepio.it

Keywords: CDC73; large genomic deletion; HPT-JT; early onset

Received: November 11, 2017     Accepted: March 20, 2018     Published: April 17, 2018

ABSTRACT

The Hyperparathyroidism with Jaw-Tumours syndrome is caused by mutations of the CDC73 gene: it has been suggested that early onset of the disease and high Ca2+ levels may predict the presence of a CDC73 mutation. We searched for large deletions at the CDC73 locus in patients with: HPT-JT (nr 2), atypical adenoma (nr 7) or sporadic parathyroid carcinoma (nr 11) with a specific MLPA and qRT-PCR assays applied on DNA extracted from whole blood. A Medline search in database for all the papers reporting a CDC73 gene mutation, clinical/histological diagnosis, age at onset, Ca2+, PTH levels for familial/sporadic cases was conducted with the aim to possibly identify biochemical/clinical markers predictive, in first diagnosis, of the presence of a CDC73 gene mutation. A novel genomic deletion of the first 10 exons of the CDC73 gene was found in a 3-generation HPT-JT family, confirmed by SNP array analysis. A classification tree built on the published data, showed the highest probability of having a CDC73 mutation in subjects with age at the onset < 41.5 years (44/47 subjects, 93.6%, had the mutation). Whereas the lowest probability was found in subjects with age at the onset ≥ 41.5 years and Ca2+ levels <13.96 mg/dL (7/20 subjects, 35.0%, had the mutation, odds ratio = 27.1, p < 0.001). We report a novel large genomic CDC73 gene deletion identified in an Italian HPT-JT family. Age at onset < 41.5 ys and Ca2+ > 13.96 mg/dL are predictive for the presence of a CDC73 genetic lesion.


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