scholarly journals RET Copy Number Alteration in Medullary Thyroid Cancer Is a Rare Event Correlated with RET Somatic Mutations and High Allelic Frequency

Genes ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 35
Author(s):  
Teresa Ramone ◽  
Chiara Mulè ◽  
Raffaele Ciampi ◽  
Valeria Bottici ◽  
Virginia Cappagli ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Copy Number ◽  
Medullary Thyroid Cancer ◽  
Rare Event ◽  
Copy Number Variations ◽  
Allelic Frequency ◽  
Medullary Thyroid ◽  
Ret Gene ◽  
Significant Difference

Copy number variations (CNV) of the RET gene have been described in 30% of Medullary Thyroid Cancer (MTC), but no information is available about their role in this tumor. This study was designed to clarify RET gene CNV prevalence and their potential role in MTC development. RET gene CNV were analyzed in 158 sporadic MTC cases using the ION Reporter Software (i.e., in silico analysis) while the multiplex ligation-dependent probe amplification assay (i.e., in vitro analysis) technique was performed in 78 MTC cases. We identified three categories of RET ploidy: 137 in 158 (86.7%) cases were diploid and 21 in 158 (13.3%) were aneuploid. Among the aneuploid cases, five out of 21 (23.8%) showed an allelic deletion while 16 out of 21 (76.2%) had an allelic amplification. The prevalence of amplified or deleted RET gene cases (aneuploid) was higher in RET positive tumors. Aneuploid cases also showed a higher allelic frequency of the RET driver mutation. The prevalence of patients with metastatic disease was higher in the group of aneuploid cases while the higher prevalence of disease-free patients was observed in diploid tumors. A statistically significant difference was found when comparing the ploidy status and mortality. RET gene CNVs are rare events in sporadic MTC and are associated with RET somatic mutation, suggesting that they could not be a driver mechanism of tumoral transformation per se. Finally, we found a positive correlation between RET gene CNV and a worse clinical outcome.

scholarly journals A Co-Occurrence of Familial Non-Medullary Thyroid Cancer and Lynch Syndrome

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A855-A855
Author(s):  
Kshama Aswath ◽  
James Welch ◽  
Sriram Gubbi ◽  
Mohammad Al Jundi ◽  
Padmasree Veeraraghavan ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Lymph Node ◽  
Medullary Thyroid Cancer ◽  
Family Members ◽  
Rare Event ◽  
Neck Lymph Node ◽  
Medullary Thyroid ◽  
Whole Exome ◽  
Node Metastases ◽  
Neck Lymph Node Metastases

Abstract Background: Lynch syndrome (LS) is an autosomal dominant disease caused by germline mutations in mismatch repair genes (MMR), leading to the early manifestation of tumors characterized by microsatellite instability (MSI) in >3 family members across at least 2 generations. MSI is a rare event in thyroid cancer (TC), occurring in up to 2.5% of sporadic cases. There is limited data on germline MMR variants’ role in familial non-medullary thyroid cancer (FNMTC). The goal of this study was to analyze the potential clinical and molecular association between LS and FNMTC. Material and Methods: We performed a cohort study analyzing the demographic, clinical, and pathologic data of 43 kindreds with FNMTC. We performed a high-throughput whole exome sequencing (WES) of peripheral-blood DNA samples of 168 participants (54 affected by FNMTC and 140 unaffected). The GATK pipeline was used in variant analysis. The NIH Institutional Review Board approved the study. Results: The study included 383 family members (104 affected, 279 unaffected) aged 43.5 [7-99] years, with 2-9 members per family affected by FNMTC. FNMTC was more prevalent in women (68.3%) and characterized by a median tumor size of 1 [0.2-5] cm, multifocal growth in 44%, gross extrathyroidal extension in 11.3%, central neck lymph node metastases in 40.3%, lateral neck lymph node metastases in 12.9% of patients, and no distant metastases. Family history screening revealed one family of Caucasian descent meeting the clinical criteria for FNMTC and LS diagnosis with 5 members affected by FNMTC and 8 individuals by Lynch-like tumors (3 with colorectal cancer/colon polyps, 2 with endometrial or ovarian tumors, 1 with kidney cancer, 1 with keratoacanthoma and 1 with unspecified Lynch-like tumors with detailed pathology report unavailable). We performed whole exome sequencing of 10 members from this family (3 affected and 7 unaffected) and remaining 158 study participants and detected exclusively in this family, a heterozygous missense variant rs373226409, in MSH2 gene c2120G>A (pCys707Tyr) in three adults affected by LS-like manifestations and two unaffected children under the age of 18 with clear segregation across three generations. This variant appears to be relatively rare with a minor allele frequency (MAF) of 0.0006 in Caucasians; however, it is more common in the South Asian population at 0.003 MAF. Immunostaining performed on the TC tumor tissue of one of the affected family members revealed intact nuclear expression of MSH2, suggestive of no major effect of the variant on MSH2 expression. Five out of seven in-silico models predicted the variant to be functionally deleterious. Conclusion: The co-occurrence of LS and FNMTC is a rare event, presenting in 2% (1/43) of families in our cohort. A common genetic association between LS and FNMTC has not been identified, and the MSH2 variant observed in this family is unlikely to be an etiologic factor.

scholarly journals Interleukin-2 and Lanreotide in the Treatment of Medullary Thyroid Cancer: In Vitro and In Vivo Studies

2013 ◽  
Vol 98 (10) ◽  
pp. E1567-E1574 ◽  
Author(s):  
Giovanni Vitale ◽  
Giovanni Lupoli ◽  
Rosario Guarrasi ◽  
Annamaria Colao ◽  
Alessandra Dicitore ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Medullary Thyroid Cancer ◽  
Interleukin 2 ◽  
In Vivo Studies ◽  
Medullary Thyroid

scholarly journals Localization of CaSR Antagonists in CaSR-expressing Medullary Thyroid Cancer

2013 ◽  
Vol 98 (11) ◽  
pp. E1722-E1729 ◽  
Author(s):  
Haiming Ding ◽  
Adlina Mohd Yusof ◽  
Shankaran Kothandaraman ◽  
Motoyasu Saji ◽  
Chaojie Wang ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Nude Mice ◽  
Medullary Thyroid Cancer ◽  
Antagonistic Activity ◽  
Parathyroid Glands ◽  
Human Embryonic Kidney Cells ◽  
Medullary Thyroid ◽  
Calcium Stimulation

Objective: Image-based localization of medullary thyroid cancer (MTC) and parathyroid glands would improve the surgical outcomes of these diseases. MTC and parathyroid glands express high levels of calcium-sensing receptor (CaSR). The aim of this study was to prove the concept that CaSR antagonists specifically localize to CaSR-expressing tumors in vivo. Design: We synthesized two isomers of a known CaSR calcilytic, Calhex 231, and four new analogs, which have a favorable structure for labeling. Their antagonistic activity was determined using immunoblots demonstrating decreased ERK1/2 phosphorylation after calcium stimulation in human embryonic kidney cells overexpressing CaSR. Compound 9 was further radiolabeled with 125I and evaluated in nude mice with and without heterotransplanted xenografts of MTC cell lines, TT and MZ-CRC-1, that do and do not express CaSR, respectively. Results: Two newly synthesized compounds, 9 and 11, exhibited better antagonistic activity than Calhex 231. The half-life of 125I-compound 9 in nude mice without xenografts was 9.9 hours. A biodistribution study in nude mice bearing both tumors demonstrated that the uptake of radioactivity in TT tumors was higher than in MZ-CRC-1 tumors at 24 hours: 0.39 ± 0.24 vs 0.18 ± 0.12 percentage of injected dose per gram of tissue (%ID/g) (P = .002), with a ratio of 2.25 ± 0.62. Tumor-to-background ratios for TT tumors, but not MZ-CRC-1 tumors, increased with time. Tumor-to-blood values increased from 2.02 ± 0.52 at 1 hour to 3.29 ± 0.98 at 24 hour (P = .015) for TT tumors, and 1.7 ± 0.56 at 1 hour to 1.48 ± 0.33 at 24 hour (P = .36) for MZ-CRC-1 tumors. Conclusions: Our new CaSR antagonists specifically inhibit CaSR function in vitro, preferentially localize to CaSR-expressing tumors in vivo, and therefore have the potential to serve as scaffolds for further development as imaging pharmaceuticals.

Extended RET Gene Analysis in Patients with Apparently Sporadic Medullary Thyroid Cancer: Clinical Benefits and Cost

2012 ◽  
Vol 3 (4) ◽  
pp. 181-186 ◽  
Author(s):  
Susan C. Lindsey ◽  
Ilda S. Kunii ◽  
Fausto Germano-Neto ◽  
Misaki Y. Sittoni ◽  
Cléber P. Camacho ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Medullary Thyroid Cancer ◽  
Gene Analysis ◽  
Medullary Thyroid ◽  
Ret Gene ◽  
Clinical Benefits

SERUM LEVEL OF DIPEPTIDYL PEPTIDASE-4 AS A POTENTIAL BIOMARKER FOR MEDULLARY THYROID CANCER

2018 ◽  
Vol 40 (4) ◽  
pp. 299-302
Author(s):  
R Abooshahab ◽  
E Niyazi ◽  
P Yaghmaie ◽  
H G Ghadaksaz ◽  
M Hedayati
Keyword(s):  
Insulin Resistance ◽  
Thyroid Cancer ◽  
Medullary Thyroid Cancer ◽  
Serum Levels ◽  
Dipeptidyl Peptidase ◽  
Control Group ◽  
Medullary Thyroid ◽  
Dipeptidyl Peptidase 4 ◽  
Potential Biomarker ◽  
Significant Difference

Aim: Adipokines are the proteins secreted from adipose tissue and play an important role in the control of metabolism. Dipeptidyl peptidase-4 (DPP4) is a novel adipokine with different biological role. As indicated by various studies, serum levels of DPP4 had been associated with body mass index (BMI), insulin resistance, metabolic syndrome and malignancy. The aim of this study was to assess the serum levels of DPP4 in patients with medullary thyroid cancer (MTC) in comparison with these in the control group. Materials and Methods: This study was performed on 45 MTC patients (24 females and 21 males) and 45 healthy controls (21 females and 24 males). DPP4 and insulin serum levels were measured by ELISA, fasting glucose serum levels by enzymecalorimetric method and insulin resistance index (HOMA-IR) by calculation using relevant equation. BMI (kg/m2) was also calculated. Results: Our data did not demonstrate a significant difference between serum DPP4 levels in MTC and healthy group (41.06 ± 22.08 ng/ml vs 39.94 ± 20.77 ng/ml, p > 0.05). Additionally, no significant difference was found in serum insulin and HOMA-IR concentrations between MTC patients and the controls (p > 0.05). Conclusions: This study suggests that the fluctuation in the levels of DPP4 does not play an important role in prognosis, early detection and diagnosis of MTC. Furthermore, higher levels of DPP4 cannot be considered as a risk factor for MTC.

RET gene mutation analysis and long-term clinical outcomes of medullary thyroid cancer patients

2020 ◽  
Vol 41 (11) ◽  
pp. 1136-1142
Author(s):  
Meghana Prabhu ◽  
Sunil Shakya ◽  
Sanjana Ballal ◽  
Shamim Ahmed Shamim ◽  
Chandrasekhar Bal
Keyword(s):  
Thyroid Cancer ◽  
Cancer Patients ◽  
Clinical Outcomes ◽  
Gene Mutation ◽  
Mutation Analysis ◽  
Medullary Thyroid Cancer ◽  
Medullary Thyroid ◽  
Ret Gene ◽  
Gene Mutation Analysis

CLM29, a multi-target pyrazolopyrimidine derivative, has anti-neoplastic activity in medullary thyroid cancer in vitro and in vivo

2014 ◽  
Vol 393 (1-2) ◽  
pp. 56-64 ◽  
Author(s):  
Alessandro Antonelli ◽  
Guido Bocci ◽  
Concettina La Motta ◽  
Silvia Martina Ferrari ◽  
Poupak Fallahi ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Medullary Thyroid Cancer ◽  
Medullary Thyroid
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