Dataset Information

Role of CDKN2C Copy Number in Sporadic Medullary Thyroid Carcinoma.

ABSTRACT:

Background

The cyclin-dependent-kinase inhibitors (CDKN)/retinoblastoma (RB1) pathway has been implicated as having a role in medullary thyroid carcinoma (MTC) tumorigenesis. CDKN2C loss has been associated with RET-mediated MTC in humans but with minimal phenotypic correlation provided. The objective of this study was to evaluate the association between tumor RET mutation status, CDKN2C loss, and aggressiveness of MTC in a cohort of patients with sporadic disease.

Methods

Tumors from patients with sporadic MTC treated at a single institution were evaluated for somatic RET^M918T mutation and CDKN2C copy number loss. These variables were compared to patient demographics, pathology detail, clinical course, and disease-specific and overall survival.

Results

Sixty-two MTC cases with an initial surgery date ranging from 1983 to 2009 met the inclusion criteria, of whom 36 (58%) were male. The median age at initial surgery was 53 years (range 22-81 years). The median tumor size was 30?mm (range 6-145?mm) with 29 (57%) possessing extrathyroidal extension. Nodal and/or distant metastasis at presentation was found in 47/60 (78%) and 12/61 (20%) patients, respectively. Median follow-up time was 10.5 years (range 1.1-27.8 years) for the censored observations. The presence of CDKN2C loss was associated with worse M stage and overall AJCC stage. Median overall survival of patients with versus without CDKN2C loss was 4.14 [confidence interval (CI) 1.93-NA] versus 18.27 [CI 17.24-NA] years (p?M918T mutation and CDKN2C loss versus no somatic RET^M918T mutation and CDKN2C loss versus somatic RET^M918T mutation and CDKN2C 2N versus no somatic RET^M918T mutation and CDKN2C 2N was 2.38 [CI 1.67-NA] years versus 10.81 [CI 2.46-NA] versus 17.24 [CI 9.82-NA] versus not reached [CI 13.46-NA] years (p?ConclusionsThe detection of somatic CDKN2C loss is associated with the presence of distant metastasis at presentation as well decreased overall survival, a relationship enhanced by concomitant RET^M918T mutation. Further defining the genes involved in the progression of metastatic MTC will be an important step toward identifying pathways of disease progression and new therapeutic targets.

SUBMITTER: Grubbs EG

PROVIDER: S-EPMC6453497 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Publications

Role of CDKN2C Copy Number in Sporadic Medullary Thyroid Carcinoma.

Grubbs Elizabeth G EG Williams Michelle D MD Scheet Paul P Vattathil Selina S Perrier Nancy D ND Lee Jeffrey E JE Gagel Robert F RF Hai Tao T Feng Lei L Cabanillas Maria E ME Cote Gilbert J GJ

Thyroid : official journal of the American Thyroid Association 20161018 11

<h4>Background</h4>The cyclin-dependent-kinase inhibitors (CDKN)/retinoblastoma (RB1) pathway has been implicated as having a role in medullary thyroid carcinoma (MTC) tumorigenesis. CDKN2C loss has been associated with RET-mediated MTC in humans but with minimal phenotypic correlation provided. The objective of this study was to evaluate the association between tumor RET mutation status, CDKN2C loss, and aggressiveness of MTC in a cohort of patients with sporadic disease.<h4>Methods</h4>Tumors ...[more]

PMID: 27610696

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Project description:Pycnodysostosis is a rare autosomal recessive skeletal dysplasia caused by a mutation in the cathepsin K encoded by cathepsin K gene (CTSK). Medullary thyroid carcinoma (MTC) is also a relatively rare type of primary thyroid carcinoma.A 31-year-old woman presenting a short stature and a palpable nodule in the front of her neck that had gradually increased in size during the last 2 years was referred to our department. She has experienced multiple fractures at lower limbs in the last 2 decades.The patient's clinical examination revealed short stature, underweight, a prominent forehead, stubby fingers, and a fixed nodule in the right thyroid lobe. Intraoral examination revealed multiple clinically malposed and missing teeth, as well as chronic periodontitis with a narrow and grooved palate. Radiographic examination revealed typical widely separated cranial sutures and an open anterior/posterior fontanel with an obtuse gonial angle, acroosteolysis, and osteosclerosis with narrowed medullary cavities. Ultrasonography of the thyroid gland showed a marked hypoechoic solid nodule in the right lobe in which tumor cell clusters were confirmed by ultrasound-guided fine needle aspiration biopsy and was suspected to be MTC. Laboratory tests revealed dramatically elevated serum calcitonin >2000?pg/L (reference range: 0-5?pg/L) and carcinoembryonic antigen (CEA) 134.37?ng/mL (reference range: 0-5?ng/mL). Genotypic screening revealed compound heterozygous mutations in the CTSK gene (c.158delA, P.Asn53Thr/c.C830T, P.Ala277Val) but no mutation associated with the familial forms of MTC.The patient underwent a total thyroidectomy with right-sided functional neck dissection.CEA and serum calcitonin decreased significantly postthyroidectomy, and no further fracture has been reported by the patient so far.The present study is the first to report a rare case of the coexistence of pycnodysostosis with a compound CTSK gene mutation and sporadic MTC. Radiological techniques and gene analysis play key roles in the definitive diagnosis.

Dataset Information

Role of CDKN2C Copy Number in Sporadic Medullary Thyroid Carcinoma.

Background

Methods

Results

Publications

Role of CDKN2C Copy Number in Sporadic Medullary Thyroid Carcinoma.

Similar Datasets

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