High frequency of alternative splicing variants of the oncogene Focal Adhesion Kinase in neuroendocrine tumors of the pancreas and breast / 医学前沿

The characteristic genetic abnormality of neuroendocrine neoplasms (NENs), a heterogeneous group of tumors found in various organs, remains to be identified. Here, based on the analysis of the splicing variants of an oncogene Focal Adhesion Kinase (FAK) in The Cancer Genome Atlas datasets that contain 9193 patients of 33 cancer subtypes, we found that Box 6/Box 7-containing FAK variants (FAK6/7) were observed in 7 (87.5%) of 8 pancreatic neuroendocrine carcinomas and 20 (11.76%) of 170 pancreatic ductal adenocarcinomas (PDACs). We tested FAK variants in 157 tumor samples collected from Chinese patients with pancreatic tumors, and found that FAK6/7 was positive in 34 (75.6%) of 45 pancreatic NENs, 19 (47.5%) of 40 pancreatic solid pseudopapillary neoplasms, and 2 (2.9%) of 69 PDACs. We further tested FAK splicing variants in breast neuroendocrine carcinoma (BrNECs), and found that FAK6/7 was positive in 14 (93.3%) of 15 BrNECs but 0 in 23 non-NEC breast cancers. We explored the underlying mechanisms and found that a splicing factor serine/arginine repetitive matrix protein 4 (SRRM4) was overexpressed in FAK6/7-positive pancreatic tumors and breast tumors, which promoted the formation of FAK6/7 in cells. These results suggested that FAK6/7 could be a biomarker of NENs and represent a potential therapeutic target for these orphan diseases.

Advances in basic and translational research in neuroendocrine neoplasms / 中华胃肠外科杂志

With the development of diagnostic techniques and the improvement of people's living standards, the detection rate of neuroendocrine tumor has been increasing and people are paying more and more attention to it. With multiple treatment modalities, the clinical research progress of neuroendocrine tumor is remarkable. However, due to the tumor heterogeneity, metastasis and recurrence of neuroendocrine tumor remains a difficult problem for clinicians. The efficacy of neuroendocrine tumor still needs to be improved. Therefore, the biological behavior of neuroendocrine tumor needs to be further studied. In recent years, with the development of molecular biology, the basic and transformation research of neuroendocrine tumor has made some progress. In this paper, we focus on the hot topics of neuroendocrine tumor, such as multiomics (copy number variation, genomics, transcriptomics), tumor microenvironment (immune microenvironment, tumor microvasculature, tumor-associated fibroblasts, etc.), preclinical research model construction (cell lines, organoids, patient derived xenograft models, genetically engineered mice), etc. Specifically, the related clinical transformation significance will be elaborated.

Genetic and epigenetic of medullary thyroid cancer

Medullary thyroid carcinoma [MTC] is an infrequent calcitonin-producing neuroendocrine tumor that initiates from the parafollicular C cells of the thyroid gland. Several genetic and epigenetic alterations are collaterally responsible for medullary thyroid carcinogenesis. In this review article, we shed light on all the genetic and epigenetic hallmarks of MTC. From the genetic perspective, RET, HRAS, and KRAS are the most important genes that are characterized in MTC. From the epigenetic perspective, Ras-association domain family member 1A, telomerase reverse transcriptase promoter methylations, overexpression of histone methyltransferases, EZH2 and SMYD3, and wide ranging increase and decrease in non-coding RNAs can be responsible for medullary thyroid carcinogenesis

Surgical treatment of pancreatic endocrine tumors in multiple endocrine neoplasia type 1

Surgical approaches to pancreatic endocrine tumors associated with multiple endocrine neoplasia type 1 may differ greatly from those applied to sporadic pancreatic endocrine tumors. Presurgical diagnosis of multiple endocrine neoplasia type 1 is therefore crucial to plan a proper intervention. Of note, hyperparathyroidism/multiple endocrine neoplasia type 1 should be surgically treated before pancreatic endocrine tumors/multiple endocrine neoplasia type 1 resection, apart from insulinoma. Non-functioning pancreatic endocrine tumors/multiple endocrine neoplasia type 1 >1 cm have a high risk of malignancy and should be treated by a pancreatic resection associated with lymphadenectomy. The vast majority of patients with gastrinoma/multiple endocrine neoplasia type 1 present with tumor lesions at the duodenum, so the surgery of choice is subtotal or total pancreatoduodenectomy followed by regional lymphadenectomy. The usual surgical treatment for insulinoma/multiple endocrine neoplasia type 1 is distal pancreatectomy up to the mesenteric vein with or without spleen preservation, associated with enucleation of tumor lesions in the pancreatic head. Surgical procedures for glucagonomas, somatostatinomas, and vipomas/ multiple endocrine neoplasia type 1 are similar to those applied to sporadic pancreatic endocrine tumors. Some of these surgical strategies for pancreatic endocrine tumors/multiple endocrine neoplasia type 1 still remain controversial as to their proper extension and timing. Furthermore, surgical resection of single hepatic metastasis secondary to pancreatic endocrine tumors/multiple endocrine neoplasia type 1 may be curative and even in multiple liver metastases surgical resection is possible. Hepatic trans-arterial chemo-embolization is usually associated with surgical resection. Liver transplantation may be needed for select cases. Finally, pre-surgical clinical and genetic diagnosis of multiple endocrine neoplasia type 1 syndrome and localization of multiple endocrine neoplasia type 1related tumors are crucial for determining the best surgical strategies in each individual case with pancreatic endocrine tumors.

Perfil de expressão gênica em carcinoma neuroendócrino produtos de insulina: avaliação da agressividade tumoral / Gene expression profiling in insulin-producing neuroendocrine carcinom: tumor aggressiveness evaluation

Insulinomas malignos correspondem entre 5-10per cent de todos os tumores de ilhota. O diagnóstico histopatológico não identifica a malignidade, somente a presença de metástase. Neste estudo foi realizada análise de expressão gênica diferencial em insulinomas com o intuito de identificar genes associados a malignidade. Foram estudados 25 pacientes com insulinoma (2 metástases). Análise de agrupamento hierárquico de alguns genes isolados reuniu os pacientes em grupos com diferentes potenciais malignos, contribuindo para melhor compreensão dos processos carcinogênicos em insulinomas / The gene expression profile associated with benign and malignant insulinomas.Five to 10 per cent insulinomas are malignant, associated with distant metastases or local invasion and histopathological diagnosis cannot identify these tumors as malignant at all. In this study differential gene expression analysis was performed in order to identify genes linked to different aggressive potentials of benign in comparison to malignant insulinomas. Twenty-five patients were studied (two metastases). Hierarchical cluster analysis of expression patterns of some isolated genes put the patients into different groups with progressive malignant potential and that may add new insights into carcinogenesis...

Identificação de genes diferencialmente expressos em tecido de paratireóide de pacientes portadores de hiperparatireoidismo primário: comparação entre hiperplasias, adenomas e carcinomas / Identification of differentially expressed genes in parathyroid tissue: comparison among hyperplasias, adenomas and carcinomas

Para identificar genes diferencialmente expressos em tecido de paratireóide, foram construídos painéis gênicos e utilizou-se a metodologia RDA . Foram isolados 13 genes que tiveram sua expressão analisada por PCR semiquantitativa em 33 amostras de tecido de pacientes portadores de hiperparatireoidismo primário, incluindo adenomas, carcinomas e hiperplasias. Os genes PTK7, RET e RAF parecem ter importante papel nos mecanismos tumorigênicos desta glândula / In order to identify differentially expressed genes in parathyroid tissue, gene panels were performed and RDA method was employed. Thirteen genes were isolated and had their expression analyzed by semi quantitative PCR in 33 tissue samples of patients with primary hyperparathyroidism, including adenomas, carcinomas and hyperplasias. The genes PTK7, RET and RAF may play an important role in the molecular mechanisms of parathyroid tumors...