CBX7 is Dualistic in Cancer Progression Based on its Function and Molecular Interactions

Chromobox protein homolog 7 (CBX7) is a member of the Chromobox protein family and participates in the formation of the polycomb repressive complex 1(PRC1). In cells, CBX7 often acts as an epigenetic regulator to regulate gene expression. However, pathologically, abnormal expression of CBX7 can lead to an imbalance of gene expression, which is closely related to the occurrence and progression of cancers. In cancers, CBX7 plays a dual role; On the one hand, it contributes to cancer progression in some cancers by inhibiting oncosuppressor genes. On the other hand, it suppresses cancer progression by interacting with different molecules to regulate the synthesis of cell cycle-related proteins. In addition, CBX7 protein may interact with different RNAs (microRNAs, long noncoding RNAs, circular RNAs) in different cancer environments to participate in a variety of pathways, affecting the development of cancers. Furthermore, CBX7 is involved in cancer-related immune response and DNA repair. In conclusion, CBX7 expression is a key factor in the occurrence and progression of cancers.

Clinical observation of a patient with TMEM127 and EGLN1 gene variants, pheochromocytoma and pancreatic tumor

Pheochromocytoma/paraganglioma is a neuroendocrine tumor of chromaffin and nonchromaffin cells of the autonomic nervous system, in most cases localized in the medullary layer of the adrenal gland. Its development is often associated with genetic predisposition. More than 30% of adult patients have genetically determined PCC/PG. In the last decade, many genes predisposing to the manifestation of PCC/PG have been found: RET, VHL, NF1, SDHB, SDHC, SDHD, SDHA, SDHAF2, TMEM127, MAH, KIF1BP, PHD2, EGLN1, FH, H-RAS, IDH, SLC25A11, MDH2. Mutation of the oncosuppressor genes TMEM127 and EGLN1, which regulate the level of factors induced by HIF hypoxia, is extremely rare in patients with PCC/PG, and has not been described at all in combination with pancreatic tumor. To date, data on the clinical manifestations of these gene mutations are limited. Accumulating clinical data on patients with identified genetic alterations is important for predicting the course of the disease, clarifying the malignant potential and stratifying the risk of developing comorbid pathology. We present the clinical case of a 62-year-old patient with PCC/PG and pancreatic tumor in whom a previously undescribed combination of TMEM127 c.99G > A (p.S33S) and EGLN1 c.515C > T (p.A172V) gene variants was found.

The Warburg Effect 97 Years after Its Discovery

The deregulation of the oxidative metabolism in cancer, as shown by the increased aerobic glycolysis and impaired oxidative phosphorylation (Warburg effect), is coordinated by genetic changes leading to the activation of oncogenes and the loss of oncosuppressor genes. The understanding of the metabolic deregulation of cancer cells is necessary to prevent and cure cancer. In this review, we illustrate and comment the principal metabolic and molecular variations of cancer cells, involved in their anomalous behavior, that include modifications of oxidative metabolism, the activation of oncogenes that promote glycolysis and a decrease of oxygen consumption in cancer cells, the genetic susceptibility to cancer, the molecular correlations involved in the metabolic deregulation in cancer, the defective cancer mitochondria, the relationships between the Warburg effect and tumor therapy, and recent studies that reevaluate the Warburg effect. Taken together, these observations indicate that the Warburg effect is an epiphenomenon of the transformation process essential for the development of malignancy.

Molecular Diagnostic of Solid Tumor Using a Next Generation Sequencing Custom-Designed Multi-Gene Panel

Next generation sequencing (NGS) allows parallel sequencing of multiple genes at a very high depth of coverage. The need to analyze a variety of targets for diagnostic/prognostic/predictive purposes requires multi-gene characterization. Multi-gene panels are becoming standard approaches for the molecular analysis of solid lesions. We report a custom-designed 128 multi-gene panel engineered to cover the relevant targets in 22 oncogene/oncosuppressor genes for the analysis of the solid tumors most frequently subjected to routine genotyping. A total of 1695 solid tumors were analyzed for panel validation. The analytical sensitivity is 5%. Analytical validation: (i) Accuracy: sequencing results obtained using the multi-gene panel are concordant using two different NGS platforms and single-gene approach sequencing (100% of 83 cases); (ii) Precision: consistent results are obtained in the samples analyzed twice with the same platform (100% of 20 cases). Clinical validation: the frequency of mutations identified in different tumor types is consistent with the published literature. This custom-designed multi-gene panel allows to analyze with high sensitivity and throughput 22 oncogenes/oncosuppressor genes involved in diagnostic/prognostic/predictive characterization of central nervous system tumors, non-small-cell lung carcinomas, colorectal carcinomas, thyroid nodules, pancreatic lesions, melanoma, oral squamous carcinomas and gastrointestinal stromal tumors.

MicroRNAs in Cancer: Small Molecules With a Huge Impact

Every cellular process is likely to be regulated by microRNAs, and an aberrant microRNA expression signature is a hallmark of several diseases, including cancer. MicroRNA expression profiling has indeed provided evidence of the association of these tiny molecules with tumor development and progression. An increasing number of studies have then demonstrated that microRNAs can function as potential oncogenes or oncosuppressor genes, depending on the cellular context and on the target genes they regulate. Here we review our current knowledge about the involvement of microRNAs in cancer and their potential as diagnostic, prognostic, and therapeutic tools.