MEN1 gene mutation with parathyroid carcinoma: first report of a familial case

Cinque, Luigia; Sparaneo, Angelo; Salcuni, Antonio Stefano; Martino, Danilo de; Battista, Claudia; Logoluso, Francesco; Palumbo, Orazio; Cocchi, R; Maiello, Evaristo; Graziano, Paolo; Hendy, Geoffrey N.; Cole, David E. C.; Scillitani, Alfredo; Guarnieri, Vito

doi:10.1530/ec-17-0207

Cited by 16 publications

(15 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Herein, one patient with AA presented with familial MEN1 syndrome characterized by AA and pituitary [30], and to date, only three cases of AA have been associated with MEN1 syndrome; two carried pathogenic variants of MEN1 [31][32][33]. MEN1 primary hyperparathyroidism is now well established owing to its role in benign parathyroid lesions or PA. Two wholeexome capture and high-throughput sequencing studies of PA revealed MEN1 alterations as a major driver, with an alteration frequency of 35% [13,14], and mutations of the gene have also been identified in AA and PC [34,35]. In this study, the MEN1 mutation occurred at a rate of 8% in PA, whereas no such alterations were detected in PC or AA.…”

Section: Discussionmentioning

confidence: 51%

Genetic Alteration Profiles and Clinicopathological Associations in Atypical Parathyroid Adenoma

Mao

et al. 2021

International Journal of Genomics

View full text Add to dashboard Cite

Genomic aberrations associated with atypical parathyroid adenoma (AA) are poorly understood. Thus, herein, we sought to expand our current understanding of the molecular basis of atypical parathyroid adenomas. We analyzed 134 samples that had been surgically obtained from parathyroid tumors, including parathyroid carcinomas, atypical parathyroid adenomas, and parathyroid adenomas. The tumors were harvested from formalin-fixed, paraffin-embedded tissues. Fifteen tumor-related genes from recently published genome sequencing data were subjected to targeted sequencing analysis, and an average sequencing depth of 500x was achieved. Sixteen (16/50, 32%) AA tumors harbored at least one of the following genomic alterations: CDC73 (12, 24%), EZH2 (4, 8%), HIC1 (1, 2%), and CDKN2A (1, 2%). Our study identified, for the first time, a relatively high frequency of genomic alterations in patients with AA in a Chinese population. This suggests that AA arises de novo, rather than developing from a parathyroid adenoma. Altogether, these findings will improve our understanding of the malignant potential of parathyroid tumors at the molecular level.

show abstract

Section: Discussionmentioning

confidence: 51%

Genetic Alteration Profiles and Clinicopathological Associations in Atypical Parathyroid Adenoma

Mao

et al. 2021

International Journal of Genomics

View full text Add to dashboard Cite

show abstract

“…This mutation is predicted to significantly decrease the protein stability of MENIN by targeting the protein for degradation [ 79 ]. The D423N mutant (D418N in isoform 2) is also exclusively found in parathyroid cancers [ 80 , 81 ]. The molecular consequence of this mutation is unexplored.…”

Section: Resultsmentioning

confidence: 99%

Comprehensive Analysis of MEN1 Mutations and Their Role in Cancer

Nelakurti

Pappula

Rajasekaran

et al. 2020

Cancers

View full text Add to dashboard Cite

MENIN is a scaffold protein encoded by the MEN1 gene that functions in multiple biological processes, including cell proliferation, migration, gene expression, and DNA damage repair. MEN1 is a tumor suppressor gene, and mutations that disrupts MEN1 function are common to many tumor types. Mutations within MEN1 may also be inherited (germline). Many of these inherited mutations are associated with a number of pathogenic syndromes of the parathyroid and pancreas, and some also predispose patients to hyperplasia. In this study, we cataloged the reported germline mutations from the ClinVar database and compared them with the somatic mutations detected in cancers from the Catalogue of Somatic Mutations in Cancer (COSMIC) database. We then used statistical software to determine the probability of mutations being pathogenic or driver. Our data show that many confirmed germline mutations do not appear in tumor samples. Thus, most mutations that disable MEN1 function in tumors are somatic in nature. Furthermore, of the germline mutations that do appear in tumors, only a fraction has the potential to be pathogenic or driver mutations.

show abstract

“…4,5 Advances in the molecular understanding of PC have described some frequent genomic alterations in PC, including in genes such as CDC73, CCND1, RB, MEN1, RET and TP53. [6][7][8][9][10][11] The major morbidity of PC usually results from intractable hypercalcemia induced by inoperable recurrent or metastatic lesions. The diagnosis of PC can be challenging, as most of the histopathologic features of PC can also be found in atypical parathyroid adenoma, unless an invasive growth pattern or distant metastases are clinically evident.…”

Section: Introductionmentioning

confidence: 99%

Preliminary exploration of potential molecular therapeutic targets in recurrent and metastatic parathyroid carcinomas

Cui

et al. 2018

Intl Journal of Cancer

View full text Add to dashboard Cite

Parathyroid carcinoma (PC) is a rare endocrine malignancy. Surgical resection is curative for local lesions, while effective therapies are lacking for recurrent or metastatic PCs. To study whether targeted therapies could be applied in recurrent or metastatic PCs, potential therapeutic targets were identified with next‐generation sequencing (NGS). DNA was extracted from formalin‐fixed, paraffin‐embedded (FFPE) sections from 19 recurrent or metastatic PC samples. A panel of 560 genes was sequenced with NGS to identify genomic alterations at an average sequencing depth of 581×. In total, 190 genomic alterations were identified. Nine PC samples (47%) harbored at least one potentially actionable genomic alteration including in the after genes: ROS1 (5/19; 26%), PTEN (3/19; 16%), TSC1 (2/19; 11%), PIK3CA (1/19; 5%), AKT1 (1/19; 5%), MTOR (1/19; 5%), ERBB2 (1/19; 5%), NTRK1 (1/19; 5%), IDH1 (1/19; 5%) and FGFR3 (1/19; 5%). CDC73 mutations were detected in 9/19 (47%) PC samples. Additional recurrent genomic alterations were identified in MSH2 (15/19; 79%), AR (9/19; 47%), BCR (8/19; 42%), SLC45A3 (6/19; 32%), MAGI1 (5/19; 26%), ZNF521 (4/19; 21%), KMT2C (4/19; 21%) and NOTCH4 (4/19; 21%). Our study identified a relatively high frequency of potentially actionable genomic alterations in PC patients in a Chinese population for the first time. A series of recurrent mutant genes was detected as well. Our study contributes to both the selection of novel targeted therapies for PC and further molecular understanding of this refractory malignancy.

show abstract

MEN1 gene mutation with parathyroid carcinoma: first report of a familial case

Cited by 16 publications

References 25 publications

Genetic Alteration Profiles and Clinicopathological Associations in Atypical Parathyroid Adenoma

Genetic Alteration Profiles and Clinicopathological Associations in Atypical Parathyroid Adenoma

Comprehensive Analysis of MEN1 Mutations and Their Role in Cancer

Preliminary exploration of potential molecular therapeutic targets in recurrent and metastatic parathyroid carcinomas

Contact Info

Product

Resources

About