scholarly journals Molecular and Other Novel Advances in Treatment of Metastatic Epithelial and Medullary Thyroid Cancers

2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
David Tai ◽  
Donald Poon
Keyword(s):  
Tumor Suppressor Genes ◽  
Somatic Mutations ◽  
Gene Mutations ◽  
C Cells ◽  
Therapeutic Approaches ◽  
Thyroid Cancers ◽  
Medullary Thyroid ◽  
Genetic Abnormalities ◽  
Pathologic Findings ◽  
Inherited Mutations

An understanding of the mutations of the proto-oncogenes and tumor suppressor genes that occur in thyroid cancers should eventually explain the diverse clinical characteristics of these tumors and also direct therapy. Some insights have already emerged in the last decade; some abnormalities in tumor genes are consistently associated with specific clinical and pathologic findings. These genetic abnormalities usually represent somatic mutations in tumors of follicular epithelial origin, as opposed to inherited mutations in medullary thyroid cancers of parafollicular C cells origin because most thyroid tumors are sporadic and not familial. This is different from the multiple endocrine neoplasia syndromes in which the primary tumorigenic gene mutations are inherited. This improved understanding of the molecular basis of these diseases has led to the development of novel targeted therapeutic approaches which will be discussed in this paper.

scholarly journals Somatic Mutations in Exons 10, 11, and 16 of the RET Protooncogene in Medullary Thyroid Carcinoma Patients

2020 ◽  
Vol 5 (3) ◽  
pp. 108-113
Author(s):  
Elham Shakiba ◽  
Mehdi Hedayati ◽  
Ahmad Majd ◽  
Monireh Movahedi
Keyword(s):  
Polymerase Chain Reaction ◽  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Somatic Mutations ◽  
Gene Mutations ◽  
Chain Reaction ◽  
Medullary Thyroid ◽  
Tumor Tissues ◽  
Polymerase Chain ◽  
Iranian Patients

Introduction: Medullary thyroid carcinoma (MTC) comprises nearly 5% of all cases of thyroid cancer (TC). Aberrant activation of RET (rearranged during transfection) signaling via somatic mutations is the basic molecular mechanism of MTC tumorigenicity. In this study, we determined the incidence of RET gene mutations in exons 10, 11, and 16 in Iranian patients. Methods: A total of 33 patients undergoing thyroidectomy at Imam Khomeini hospital of Tehran, Iran and diagnosed with MTC were enrolled. For investigating mutations in exons 10, 11, and 16, DNA was extracted from tumor tissues, and the genes were amplified by polymerase chain reaction (PCR) and then sequenced. Results: Out of 33 patients, 20 (60.6%) subjects had mutations in one of the examined exons (10, 11, and 16). According to our results, the "ATG918ACG" mutation in codon 918 had the highest rate. Conclusion: Testing RET mutations can be beneficial in clinical evaluation and treatment management of MTC patients.

Thyroid cancer

2020 ◽  
pp. 2302-2312
Author(s):  
Kristien Boelaert ◽  
Anthony P. Weetman
Keyword(s):  
Thyroid Cancer ◽  
Cell Cancer ◽  
Point Mutations ◽  
C Cells ◽  
Thyroid Cancers ◽  
Medullary Thyroid ◽  
Local Pain ◽  
Thyroid Mass ◽  
Follicular Epithelial Cell ◽  
Well Differentiated

Thyroid cancers are the most common endocrine malignancies and their incidence is rising globally, largely due to significant increases in small, incidentally detected low-risk tumours. Follicular epithelial cell cancer is the commonest type; this usually presents with usually well differentiated tumours and has an excellent prognosis, but occasionally highly undifferentiated; it may be induced by exposure to ionizing radiation. Medullary thyroid carcinoma arises from parafollicular C cells; it comprises 3–5% of all thyroid cancers; usually hereditary autosomal dominant forms associated with germline point mutations in the RET proto-oncogene. Rare thyroid tumours include anaplastic carcinomas, which present as a rapidly enlarging and fixed thyroid masses, sometimes with local pain; they are rapidly fatal; sarcomas; and primary lymphomas—these usually present as a rapidly enlarging thyroid mass in a patient with Hashimoto’s thyroiditis.

scholarly journals Exomic Sequencing of Medullary Thyroid Cancer Reveals Dominant and Mutually Exclusive Oncogenic Mutations in RET and RAS

2013 ◽  
Vol 98 (2) ◽  
pp. E364-E369 ◽  
Author(s):  
Nishant Agrawal ◽  
Yuchen Jiao ◽  
Mark Sausen ◽  
Rebecca Leary ◽  
Chetan Bettegowda ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Somatic Mutations ◽  
Medullary Thyroid Cancer ◽  
Driver Mutations ◽  
High Confidence ◽  
Kras Mutations ◽  
Protein Coding ◽  
Medullary Thyroid ◽  
Oncogenic Mutations ◽  
Independent Cohort

Abstract Context: Medullary thyroid cancer (MTC) is a rare thyroid cancer that can occur sporadically or as part of a hereditary syndrome. Objective: To explore the genetic origin of MTC, we sequenced the protein coding exons of approximately 21,000 genes in 17 sporadic MTCs. Patients and Design: We sequenced the exomes of 17 sporadic MTCs and validated the frequency of all recurrently mutated genes and other genes of interest in an independent cohort of 40 MTCs comprised of both sporadic and hereditary MTC. Results: We discovered 305 high-confidence mutations in the 17 sporadic MTCs in the discovery phase, or approximately 17.9 somatic mutations per tumor. Mutations in RET, HRAS, and KRAS genes were identified as the principal driver mutations in MTC. All of the other additional somatic mutations, including mutations in spliceosome and DNA repair pathways, were not recurrent in additional tumors. Tumors without RET, HRAS, or KRAS mutations appeared to have significantly fewer mutations overall in protein coding exons. Conclusions: Approximately 90% of MTCs had mutually exclusive mutations in RET, HRAS, and KRAS, suggesting that RET and RAS are the predominant driver pathways in MTC. Relatively few mutations overall and no commonly recurrent driver mutations other than RET, HRAS, and KRAS were seen in the MTC exome.

scholarly journals A Review of the Significance in Measuring Preoperative and Postoperative Carcinoembryonic Antigen (CEA) Values in Patients with Medullary Thyroid Carcinoma (MTC)

Medicina ◽  
2021 ◽  
Vol 57 (6) ◽  
pp. 609
Author(s):  
Ioannis Passos ◽  
Elisavet Stefanidou ◽  
Soultana Meditskou-Eythymiadou ◽  
Maria Mironidou-Tzouveleki ◽  
Vasiliki Manaki ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Carcinoembryonic Antigen ◽  
Medullary Thyroid Carcinoma ◽  
Clinical Significance ◽  
Relevant Literature ◽  
Distant Metastases ◽  
Lymph Node Involvement ◽  
C Cells ◽  
Gastrointestinal Malignancies ◽  
Medullary Thyroid

Background and Objectives: Medullary thyroid carcinoma (MTC) accounts for 1–2% of all thyroid malignancies, and it originates from parafollicular “C” cells. Carcinoembryonic antigen (CEA) is a tumor marker, mainly for gastrointestinal malignancies. There are references in literature where elevated CEA levels may be the first finding in MTC. The aim of this study is to determine the importance of measuring preoperative and postoperative CEA values in patients with MTC and to define the clinical significance of the correlation between CEA and the origin of C cells. Materials and Methods: The existing and relevant literature was reviewed by searching for articles and specific keywords in the scientific databases of PubMedCentraland Google Scholar (till December 2020). Results: CEA has found its place, especially at the preoperative level, in the diagnostic approach of MTC. Preoperative CEA values >30 ng/mL indicate extra-thyroid disease, while CEA values >100 ng/mL are associated with lymph node involvement and distant metastases. The increase in CEA values preoperatively is associated with larger size of primary tumor, presence of lymph nodes, distant metastases and a poorer prognosis. The clinical significance of CEA values for the surgeon is the optimal planning of surgical treatment. In the recent literature, C cells seem to originate from the endoderm of the primitive anterior gut at the ultimobranchial bodies’ level. Conclusions: Although CEA is not a specific biomarker of the disease in MTC, itsmeasurement is useful in assessing the progression of the disease. The embryonic origin of C cells could explain the increased CEA values in MTC.

scholarly journals Epigenetic events in medulloblastoma development

2005 ◽  
Vol 19 (5) ◽  
pp. 1-13 ◽  
Author(s):  
Janet C. Lindsey ◽  
Jennifer A. Anderton ◽  
Meryl E. Lusher ◽  
Steven C. Clifford
Keyword(s):  
Gene Expression ◽  
Tumor Suppressor Genes ◽  
Molecular Basis ◽  
Gene Disruption ◽  
Functional Role ◽  
Promoter Hypermethylation ◽  
Therapeutic Approaches ◽  
Primary Tumors ◽  
Molecular Events ◽  
Epigenetic Events

Over the last decade, the analysis of genetic defects in primary tumors has been central to the identification of molecular events and biological pathways involved in the pathogenesis of medulloblastoma, the most common malignant brain tumor of childhood. Despite this, understanding of the molecular basis of the majority of cases remains poor. In recent years, the emerging field of epigenetics, which describes heritable alterations in gene expression that occur in the absence of DNA sequence changes, has forced a revision of the understanding of the mechanisms of gene disruption in cancer. Accumulating evidence indicates a significant involvement for epigenetic events in medulloblastoma development. Recent studies have identified a series of candidate tumor suppressor genes (for example, RASSF1A, CASP8, and HIC1) that are each specifically epigenetically inactivated in a large proportion (> 30%) of medulloblastomas by promoter hypermethylation, leading to the silencing of their gene expression. These findings shed new light on medulloblastoma and offer great potential for an improved understanding of its molecular pathology. The authors review the current understanding of epigenetic events in cancer and their contribution to medulloblastoma development. Their nature, origins, and functional role(s) in tumorigenesis are considered, and the authors assess the potential utility of these events as a basis for novel diagnostic and therapeutic approaches.

New Multiple Somatic Mutations in the RET Proto-oncogene Associated with a Sporadic Medullary Thyroid Carcinoma

Thyroid ◽  
2006 ◽  
Vol 16 (3) ◽  
pp. 311-316 ◽  
Author(s):  
Š. Dvořáková ◽  
E. Václavíková ◽  
V. Sýkorová ◽  
J. Dušková ◽  
P. Vlček ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Somatic Mutations ◽  
Sporadic Medullary Thyroid Carcinoma ◽  
Medullary Thyroid

Selpercatinib for lung and thyroid cancers with RET gene mutations or fusions

2021 ◽  
Vol 57 (10) ◽  
pp. 621
Author(s):  
H. Zheng ◽  
Z.-S. Chen ◽  
J. Li
Keyword(s):  
Gene Mutations ◽  
Thyroid Cancers ◽  
Ret Gene

Expression of laminin-2 by normal and neoplastic rat C cells during the development of medullary thyroid carcinoma

1999 ◽  
Vol 434 (4) ◽  
pp. 325-332 ◽  
Author(s):  
Fatima Lekmine ◽  
Hélène Feracci ◽  
Gérard Milhaud ◽  
Françoise Treilhou-Lahille ◽  
N. Jeanne
Keyword(s):  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
C Cells ◽  
Medullary Thyroid

scholarly journals Cardiac Metastasis from Medullary Thyroid Cancers with Long-Term Survival under Vandetanib

2021 ◽  
pp. 1-6
Author(s):  
Camille Buffet ◽  
Sophie Leboulleux ◽  
Françoise Kraeber-Bodéré ◽  
Caroline Bodet-Milin ◽  
Laure Cabanes ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Surgical Excision ◽  
Cardiac Metastasis ◽  
Term Survival ◽  
Long Term Survival ◽  
Thyroid Cancers ◽  
Medullary Thyroid ◽  
Cardiac Metastases

<b><i>Background:</i></b> Cardiac metastases from thyroid cancers are uncommon with a poor prognosis. There is a lack of long-term follow-up studies. <b><i>Cases:</i></b> We report 2 cases of cardiac metastasis from medullary thyroid cancer (MTC). Both patients presented limited metastatic disease apart from a cardiac metastasis. The initial diagnosis was challenging and was facilitated by functional imaging with an immuno-PET-CT using an anti-CEA bispecific antibody and a <sup>68</sup>Ga-labeled peptide. Both patients were treated with the multitarget kinase inhibitor vandetanib with prolonged stability. The first patient was alive at the last follow-up, 14 years after the diagnosis of cardiac metastasis. The second patient required surgical excision of the cardiac mass because of disease progression under vandetanib. <b><i>Conclusion:</i></b> These cases illustrate long-term survival and effectiveness of clinical management of 2 patients who developed cardiac metastases from MTC, in the current era of personalized medicine with targeted therapy.

scholarly journals Non-invasive detection of urothelial cancer through the analysis of driver gene mutations and aneuploidy

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Simeon U Springer ◽  
Chung-Hsin Chen ◽  
Maria Del Carmen Rodriguez Pena ◽  
Lu Li ◽  
Christopher Douville ◽  
...  
Keyword(s):  
Urothelial Cancer ◽  
Gene Mutations ◽  
Driver Gene ◽  
Low Grade ◽  
Invasive Approach ◽  
Non Invasive ◽  
Genetic Abnormalities ◽  
Patients At Risk ◽  
Upper Tract Urothelial Cancer ◽  
Copy Number Changes

Current non-invasive approaches for detection of urothelial cancers are suboptimal. We developed a test to detect urothelial neoplasms using DNA recovered from cells shed into urine. UroSEEK incorporates massive parallel sequencing assays for mutations in 11 genes and copy number changes on 39 chromosome arms. In 570 patients at risk for bladder cancer (BC), UroSEEK was positive in 83% of those who developed BC. Combined with cytology, UroSEEK detected 95% of patients who developed BC. Of 56 patients with upper tract urothelial cancer, 75% tested positive by UroSEEK, including 79% of those with non-invasive tumors. UroSEEK detected genetic abnormalities in 68% of urines obtained from BC patients under surveillance who demonstrated clinical evidence of recurrence. The advantages of UroSEEK over cytology were evident in low-grade BCs; UroSEEK detected 67% of cases whereas cytology detected none. These results establish the foundation for a new non-invasive approach for detection of urothelial cancer.

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