Cancer Genetics最新文献

The nuclear pore complexes are essential for cellular and molecular processes such as trafficking between the cytoplasm and the nucleus, chromatin, transcriptional outputs, and DNA damage repair. Nucleoporins, components of nuclear pore complexes, have been linked to cancer through nucleo-cytoplasmic cargo trafficking, cell division, signalling pathways, chromatin-related processes, and protein stability and degradation. This study aims to understand how nucleoporins specifically contribute to cancer proliferation and progression across various cancer types. Accordingly, angles such as nuclear trafficking, fusion proteins, tumour suppressors, signalling pathways, tumour microenvironment, nucleosomes, and chromatin processes were found to bridge the function of nucleoporins and cancer progression, and the underlying mechanisms have been analysed in this study. A deep understanding of the function of nucleoporins in cancer progression will pave the way for the effective targeting of these molecules for therapeutic gain. Improved treatment responses can enhance the quality of life of cancer patients.

Few reports have analyzed the fusion genes involved in carcinogenesis in the oropharynx, where the incidence of human papillomavirus-associated tumors is relatively low. The aim of this study was to identify novel driver fusion genes in patients with oropharyngeal cancer. The study enrolled fifty-seven patients who were diagnosed with oropharyngeal carcinoma. RNA sequencing data from fresh-frozen specimens were used to identify candidate fusion genes via the JAFFA, arriba, and STAR-Fusion pipelines. Candidate fusion genes were confirmed by direct sequencing. The expression level of a candidate fusion gene was compared to that of tumors without fusion genes. Finally, filtering was performed for driver genes using the annoFuse pipeline. In addition, the VIRTUS pipeline was used to analyze the presence of human papillomavirus in the tumors. We identified 5 (8.8 %) novel potential driver in-frame fusion genes, MKNK2::MOB3A, ICMT::RPS6KA3, ATP1B3::GRK7, CSNK2A1::KIF16B, and FGFR3::MAEA, and 1 (1.8 %) known in-frame fusion gene, FGFR3::TACC3, in 57 patients with pharyngeal carcinoma. Our results suggest that sporadic fusion genes may contribute to tumorigenesis in oropharyngeal carcinomas.

Objectives

The International Consensus Classification (ICC) and 5th Edition of the World Health Organization Classification (WHO-5) made substantive updates to the classification of myeloid neoplasms. This study compares the systems in a series of myeloid neoplasms with increased blasts, analyzing implications for diagnostic workflow and reporting.

Methods

Bone marrow biopsies categorized as myelodysplastic syndrome with excess blasts (MDS-EB) or acute myeloid leukemia (AML) by WHO-R4 were identified. Results of morphology review, karyotype, fluorescence in situ hybridization, and next-generation sequencing were compiled. Cases were retrospectively re-classified by WHO-5 and ICC.

Results

46 cases were reviewed. 28 cases (61 %) had ≥20 % blasts, with the remaining cases having 5–19.5 % blasts. The most common differences in classification were 1) the designation of MDS versus MDS/AML (10/46, 22 %) for cases with 10–19 % blasts and 2) the ICC's designation of TP53 variants as a separate classifier for AML (8/46, 17 %). Bi-allelic/multi-hit TP53 alterations were identified in 15 cases (33 %). Variants of potential germline significance were identified in 29 (63 %) cases.

Conclusions

While terminology differences between WHO-5 and ICC exist, both systems invoke similar opportunities for improved reporting: standardized classification of pathogenic variants (notably TP53), streamlined systems to evaluate for potential germline variants, and integrated reporting of morphologic and genetic data.

There is a rich history of cancer treatments which provides a number of important lessons for present and future cancer therapies. We outline this history by looking in the past, reviewing the current landscape of cancer treatments, and by glancing at the potential future cancer therapies.

Breast cancer has distinct causes and molecular characteristics at premenopausal and postmenopausal ages. The age-standardized incidence rate for postmenopausal breast cancer is more than 10 times higher than in premenopausal breast cancer. Here, we showed that the expression of 10 out of 20 most frequently mutated genes in breast cancer (namely, PIK3CA, CDH1, MUC16, PTEN, FAT3, FAT1, SPEN, ARID1A, LRP1B and RUNX1) is higher in premenopausal women with breast cancer than in postmenopausal women with breast cancer. The most significant differences in the expression in terms of menopause status were observed for RUNX1 and FAT1. Furthermore, we found that the majority of these 10 genes also show ER (estrogen receptor) or PR (progesterone receptor) status-dependent expression in both premenopausal and postmenopausal breast cancer patients. Unlike what we observed in the case of ER or PR status, the expression of most of these genes does not change depending on HER2 (human epidermal growth factor receptor 2) status in both premenopausal and postmenopausal breast cancer patients. Combined, our analysis suggests that menopause status might influence the expression of most frequently mutated genes in breast cancer, and that the most of these genes whose expression differ between pre- and post-menopausal women with breast cancer also show ER or PR status-dependent expression in women with breast cancer.

Colon cancer (CC) is a common malignancy over the world and its morbidity and mortality significantly went up in China in recent years. Molecular functions in cancers have gradually been the pivot subject in cancer research. Neuroepithelial cell transforming 1 (NET1) was reported to contribute to prostate cancer and gastric cancer. Our study figured out that NET1 was overexpressed in CC cells. Then, loss-of-function assays revealed that NET1 facilitated CC cell proliferation and repressed CC cell apoptosis. Next, miR-338–3p was confirmed to target NET1. After that, we verified that circ_0017552 which originates from NET1 could positively modulate NET1 expression. Besides, circ_0017552 was a sponge of miR-338–3p. Rescue assays’ results demonstrated that circ_0017552 could regulate CC cell proliferation and apoptosis through up-regulation of NET1. A transcription factor named Sp1 (SP1) was found to be present in circ_0017552. SP1 induced transcription of circ_0017552 to facilitate CC cell proliferation and inhibit CC cell apoptosis. In a word, SP1-induced circ_0017552 regulated CC cell proliferation and apoptosis through miR-338–3p/NET1 axis.

Although lncRNAs are recognized to contribute to the development of oral squamous-cell carcinoma (OSCC), their exact function in invasion and cell migration is not clear. In this research, we explored the molecular and cellular mechanisms of FOXD2-AS1 in OSCC. Prognostic and bioinformatics analyses were used to test for the differential expression of FOXD2-AS1-PLOD1. Following FOXD2-AS1 suppression or overexpression, changes in cell viability were measured using the CCK-8 test; changes in cell migration and invasion abilities were measured using the migration and the Transwell assay. The expression of associated genes and proteins was found using Western blot and RT-qPCR. Analysis of luciferase reporter genes was done to look for regulatory connections between various molecules. The FOXD2-AS1-PLOD1 pair, which was highly expressed in OSCC, was analyzed and experimentally verified to be closely related to the prognosis of OSCC, and a nomogram model and correction curve were constructed. The inhibition of FOXD2-AS1 resulted in the reduction of cell activity, migration, invasion ability and changes in genes related to invasion and migration. In vivo validation showed that inhibition of FOXD2-AS1 expression slowed tumor growth, and related proteins changed accordingly. The experiments verified that FOXD2-AS1 negatively regulated miR-185–5 p and that miR-185–5 p negatively regulated PLOD1. In addition, it was found that the expression of PLOD1, p-Akt and p-mTOR proteins in OSCC cells was reduced by the inhibition of FOXD2-AS1, and FOXD2-AS1 and PLOD1 were closely related to the Akt/mTOR pathway. Increased expression of FOXD2-AS1 promotes OSCC growth, invasion and migration, which is important in part by targeting miR-185–5 p/PLOD1/Akt/mTOR pathway activity.