Медицинская литература. Новинки

 

 

 

 

 

 

Молекулярно-генетическая структура фолликулярно-клеточного рака щитовидной железы

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Рак щитовидной железы лидирует по частоте среди злокачественных новообразований эндокринной системы. В большинстве случаев опухолевые клетки имеют фолликулярно-клеточное происхождение. Диагностика рака основана на проведении цитологического анализа биоптатов узлов щитовидной железы, точность которого не превышает 80%. Это ведет как к ложноположительным, так и ложноотрицательным диагнозам и выбору неправильной тактики лечения. Выявление в биоптатах генетических и эпигенетических маркеров рака щитовидной железы позволит повысить точность диагноза. В данной статье описаны мутации, аберрантное метилирование ДНК и аберрантная экспрессия микроРНК, составляющие основу молекулярно-генетической структуры фолликулярно-клеточного рака щитовидной железы. Мутации, характерные для данного типа рака щитовидной железы, включают точковые, хромосомные перестройки и изменение числа копий генов. Помимо распространенных и хорошо описанных драйверных мутаций генов сигнальных путей МАРK, PI3K/Akt и Wnt, а также генов TP53 иTERT, в данной работе приведены более редкие мутации, выявленные за последние два года. В статье также представлены примеры использования диагностических панелей, основанных на анализе молекулярно-генетических маркеров.

Ключевые слова:
рак щитовидной железы, папиллярный РЩЖ, фолликулярный РЩЖ, мутации, перестройки, метилирование ДНК, микроРНК, KRAS, KRAF, BRAF, thyroid cancer, PTC, FTC, mutations, fusions, DNA methylation, microRNA, KRAS, KRAF, BRAF

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Molecular genetics of follicular cell thyroid carcinoma

Thyroid cancer is the most frequent endocrine malignancy. In the most cases thyroid cancer arises from follicular cells. Diagnosis of the cancer is based on the cytological analysis of fine needle aspiration biopsy of thyroid nodes. But the accuracy of the cytological diagnosis is about 80% that leads to the false positive and false negative cases and wrong strategy of treatment. Identification of genetic and epigenetic markers in the biopsies will allow to improve diagnostic accuracy. This article describes mutations, aberrant DNA methylation and abnormal microRNA expression constituting the core of molecular genetics of follicular cell thyroid cancer. The mutations given in the article includes point mutations, fusions and copy number variation. Besides frequent and well described driver mutations in genes of МАРK, PI3K/Akt and Wnt signaling pathways, as well as TP53 and TERT genes, we introduce here less frequent mutations appeared in the literature during the past two years. In addition the article contains examples of diagnostic panels applying these markers.

Keywords:
рак щитовидной железы, папиллярный РЩЖ, фолликулярный РЩЖ, мутации, перестройки, метилирование ДНК, микроРНК, KRAS, KRAF, BRAF, thyroid cancer, PTC, FTC, mutations, fusions, DNA methylation, microRNA, KRAS, KRAF, BRAF