{"id":1593,"date":"2026-01-24T08:35:20","date_gmt":"2026-01-24T08:35:20","guid":{"rendered":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/2026\/01\/24\/defects-of-dna-repair-pathway-occur-in-medullary-thyroid-carcinoma\/"},"modified":"2026-01-24T08:35:20","modified_gmt":"2026-01-24T08:35:20","slug":"defects-of-dna-repair-pathway-occur-in-medullary-thyroid-carcinoma","status":"publish","type":"post","link":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/2026\/01\/24\/defects-of-dna-repair-pathway-occur-in-medullary-thyroid-carcinoma\/","title":{"rendered":"DEFECTS OF DNA REPAIR PATHWAY OCCUR IN MEDULLARY THYROID CARCINOMA"},"content":{"rendered":"
Lei Ye1<\/sup>, Libero Santarpia1<\/sup>, GilbertJ. Cote1<\/sup>, Adel K. EI-Naggar2<\/sup>, Robert F. Gagel1<\/sup><\/div>\n
1<\/sup>Department of Endocrine Neoplasia & Hormonal Disorders, 2<\/sup>DepartmentofPathology, University of Texas, M. D.Anderson Cancer Center, Houston, USA.<\/div>\n
Background:<\/strong> DNA repair genes play a critical role in the maintenance of genomic integrity and their disruption is a known mechanism for tumorigenesis. Chromosome instability has been observed in patients with medullary thyroid carcinomas (MTC). <\/p>\n

Aim:<\/strong> The purpose of this study was to perform a systematic examination of whether DNA repair dysfunction occurs in MTC <\/p>\n

Methods:<\/strong> We used high density array-CGH to detect allelic loss of DNA repair genes in the genomic DNA isolated from 20 primary sporadic tumor samples. Our survey included 152 genes involved in the major pathways for DNA repair. A subset of genes with CGH-detected losses were confirmed by qPCR. DNA sequencing analysis and protein expression studies are currently being performed in tumor tissues to identify loss of function. <\/p>\n

Results:<\/strong> Four genes showed consistent allelic loss in greater than 30% of the tumors.This included RADI7(DNA damage sensors); CHEK2 (signal transducer); XRCC2 (homologous recombination) and XRCC6 (DNA nonhomologous end-joining). Overall, 65% tumors examined had allelic loss of at least one gene. Tumors derived from patients with either lymph node or distant metastases had a higher frequency of allelic loss of these DNA repair genes compared with non-metastatic tumors (79% vs 33%, p=0.05). No significant correlation was found between DNA repair gene loss and RET status, tumor size, or age of onset. Despite an absense of coding region mutations, a reduced level of CHEK2 protein was observed in metastatic tumors compared with the primary tumors.

Conclusion:<\/strong> Our findings are the first to associate allelic loss of DNA repair genes with transformation of the parafollicular cell. They provide a plausible explanation for the genomic instability associated with this tumor. The specific association of metastasis potential with down regulation of CHEK2 suggests that defects of DNA repair pathway could influence the progression of MTC and may provide for the development of novel therapeutic targets. <\/p>\n

References: <\/strong><\/p>\n

1. http:\/\/www.cgal.icnet.uklDNA_Repair_Genes.html
2. HsuTC, Pathak S, Samaan N, Hickey RC. Chromosome instability in patients with medullary carcinoma of the thyroid. JAMA. 1981 246:2046-8.<\/div>\n","protected":false},"excerpt":{"rendered":"

Lei Ye1, Libero Santarpia1, GilbertJ. Cote1, Adel K. EI-Naggar2, Robert F. Gagel1 1Department of Endocrine Neoplasia & Hormonal Disorders, 2DepartmentofPathology, University of Texas, M. D.Anderson Cancer Center, Houston, USA. Background: DNA repair genes play a critical role in the maintenance of genomic integrity and their disruption is a known mechanism for tumorigenesis. Chromosome instability has Read More<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[52,2,11],"tags":[],"class_list":["post-1593","post","type-post","status-publish","format-standard","hentry","category-volume-9-issue-2","category-journal-articles","category-volume-9"],"_links":{"self":[{"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/posts\/1593","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/comments?post=1593"}],"version-history":[{"count":0,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/posts\/1593\/revisions"}],"wp:attachment":[{"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/media?parent=1593"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/categories?post=1593"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/tags?post=1593"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}