Mutations In Other Related Genes Research Articles

Фенокопии синдрома множественных эндокринных неоплазий 1-го типа — возможные причины

Multiple endocrine neoplasia type 1 (MEN-1) is a rare autosomal dominant disorder resulting from mutations in the MEN1 gene, which codes for the menin protein. This syndrome is marked by the development of tumors in the parathyroid glands, gastroenteropancreatic neuroendocrine tumors, pituitary adenomas, alongside other endocrine and non-endocrine tumors. In 5–10% of individuals exhibiting symptoms of MEN-1, no mutations are detected in the MEN1 gene; this clinical picture is classified as phenocopy syndrome. In such instances, mutations may reside in unexamined regions of the MEN1 gene, or alternative gene silencing mechanisms and mutations in other related genes may contribute to MEN1-associated tumor pathogenesis. Identifying a genetically confirmed MEN-1 syndrome in patients manifesting MEN-1 symptoms is essential for evaluating tumor development risks and optimizing follow-up protocols. This is particularly important since patients with genetically confirmed MEN-1 syndrome generally face a reduced life expectancy compared to the broader population and experience a more aggressive disease progression than those with clinical manifestations of the syndrome without identifiable mutations. KEYWORDS: multiple endocrine neoplasia type 1, phenocopy, genetics, epigenetics. FOR CITATION: Trukhina D.A., Mamedova E.O., Belaya Zh.E., Melnichenko G.A. Possible causes of phenocopy syndrome in multiple endocrine neoplasia type 1. Russian Medical Inquiry. 2024;8(9):526–530 (in Russ.). DOI: 10.32364/2587-6821-2024-8-9-4

The lack of correlation between TP53 mutations and gastric cancer: A report from a province of Iran

Gastric cancer ranks second cause of cancer death worldwide after lung cancer. Its etiology is heterogeneous and genetic factors including protooncogenes and tumor suppressor genes always contribute to the progression of cancer. The TP53 tumor suppressor gene has a broad role in genomic stability and DNA repair. The aim of this study was to determine the TP53 gene mutations in gastric cancer specimens in Chaharmahal Va Bakhtiari province of Iran. In this descriptive-lab based study, we investigated the promoter and exons of TP53 gene mutations in 38 paraffin-embedded gastric cancer specimens. DNA was extracted following a standard phenol-chloroform protocol. The TP53 gene mutations were determined using PCR-SSCP & PCR-RFLP procedures. The present study revealed no TP53 gene mutation in the promoter and exons in the gastric cancer subjects studied. While TP53 gene mutations have been reported as the most frequent genetic alterations and are found in about 50% of the human malignancies, no mutation was detected in this study. This may be due to mutations in other related genes in the same pathway or epigenetic factors.

Merkel cell carcinoma: evaluation of KIT (CD117) expression and failure to demonstrate activating mutations in the C‐KIT proto‐oncogene – implications for treatment with imatinib mesylate

Merkel cell carcinomas (MCCs) express the tyrosine kinase receptor KIT. However, it is not known if MCCs have activating mutations in KIT that would make them responsive to treatment with imatinib mesylate. The purpose of this article is to describe the KIT immunohistological staining pattern (CD117) of MCCs and analyze those MCCs for mutations in areas of KIT where mutations are found in gastrointestinal stromal cell tumors. We evaluated KIT immunostaining in nine MCCs from nine patients. In addition, we extracted DNA from the same MCCs, performed PCR amplification of C-KIT exons 9, 11, 13, and 17, and sequenced those gene products for mutations. Eight of nine (88.8%) MCCs expressed KIT. No mutations were found. The majority of MCCs express KIT but do not contain activating mutations in exons 9, 11, 13, or 17 of KIT. Imatinib mesylate is unlikely to provide effective therapy in MCC unless activating mutations in other areas of KIT or activating mutations in other related genes can be detected.