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Familial Multiple Myeloma
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Chromosome abnormalities and genetic mutations alter chromosomal copy numbers, change gene expression signatures, and induce secondary mutations [e.g., gain(1q), del(1p), del(17p), del(13), RAS mutations, secondary translocations involving MYC], leading to gain of function in K-Ras, N-Ras, FAM46C, MYC, and BRAF, loss of function in p53, deregulation of the RAS/MAPK/NF-κB pathway, epigenetic changes with histone methylation/deacetylation, and genomic instability within multiple myeloma cells. In fact, overexpression of MYC associated with chromosomal rearrangement is a force driving the shift from MGUS to multiple myeloma [1,2].
Multiple Myeloma
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Genetic events include translocations, loss of heterozygosity, gene amplification, gene mutation, and as yet poorly understood epigenetic changes, and establishing correlates between abnormalities and clinical outcome has been difficult. Translocations involving chromosome 14q32 occur in 50% of cases, and these usually involve the heavy chain switch regions of the IgH gene although recently breakpoints involving VDJ have been described. These translocations occur in all cells of the clone and at the MGUS stage and are felt to be an initiating event. Several partner chromosomes have been identified with breakpoints frequently near the site of cellular protooncogenes, e.g. cyclin D1 on 11q13, fibroblast growth factor receptor 3 (FGFR3) and MMSET on 4p16, CCND3 on chromosome 6p21, and MAF genes on chromosome 16q23. The t(4;14) translocation occurs in 15% of cases and is associated often with an IgA M-protein and a poor outcome possibly partly overcome with bortezomib-based therapy. Due to the reciprocal nature of this translocation, two oncogenes are activated, FGR3 and MMSET, although their exact contributions remain controversial. The t(11;14) with overexpression of cyclin D1 is associated with an intermediate prognosis, and sensitivity to bcl-2 inhibition (venetoclax) with often lymphoplasmacytoid morphology and CD20 expression. About 20% of myelomas have a unique non-recurrent partner chromosome translocating to 14q32. Myeloma lacking an IgH translocation tends to have hyperdiploidy although there is some overlap between the two groups and hyperdiploidy is associated with a better prognosis. Similar to IgH translocations, hyperdiploidy is an early event found in MGUS stage and is characterized by multiple trisomies typically involving the odd-numbered chromosomes (i.e. 3, 5, 7, 9, 11, 15, 19, 21). Loss of 13q is common, occurring in 58% of myelomas, involves loss of the Rb gene, although homozygous loss or inactivation is not common, and co-associates with other poor prognostic markers such as t(4;14). Chromosome 1q gain and loss of chromosome 1p (probably affecting CDKN2C and FAM46C genes) are poor prognostic events although the relevant genes affected on 1q are not clear. Loss of tumor suppressor genes requires inactivation of both alleles and a number of genes have been identified as being relevant as tumor suppressor genes in myeloma including BIRC2, TRAF3, FAM46C, and DIS3.
Traditional Chinese Medicine in Oncotherapy: The Research Status
Published in Nutrition and Cancer, 2020
Huijuan Tang, Peng Shu, Shenlin Liu, Xu Zhang, Monica Mattioli-Belmonte
Even when the effects of chemotherapy and radiation are significant, many patients will lose their lives due to recurrence and metastasis. Research has found that geranyl lignin (from the Citrus limon) through matrix metalloproteinase (MMP) pathway could inhibit the expression of MMP-2 and MMP-9 protein levels and reduce the hydrolysis of the extracellular matrix, and the extracellular matrix has powerful resistance to invasion and metastasis in liver cancer (46). FAM46C plays a critical role in migration and invasion of hepatocellular carcinoma cells via TGF-β/Smad signaling. Norcantharidin (a cantharidin derivative, from Lytta vesicatoria) could antimetastatic by upregulating FAM46C expression and regulating TGF-β/Smads signaling pathway which prevents the expression of EMT-related transcription factors (47). Berberine (from Coptis chinensis) can significantly inhibit the extracorporeal and internal migration of HCT-116 cells in CRC by regulating the Ras-ERK signaling pathway (48).
Microanatomy of the metabolic associated fatty liver disease (MAFLD) by single-cell transcriptomics
Published in Journal of Drug Targeting, 2023
Lijun Wang, Kebing Zhou, Qing Wu, Lingping Zhu, Yang Hu, Xuefeng Yang, Duo Li
It is well-established that the cell type can be identified according to the marker gene of the cell type. For example, the marker genes of endothelial cells, T cells, Kupffer cells, B cells, macrophages, dendritic cells, cholangiocytes, hepatocytes, Plasma B cells, and hepatic stellate cells (HSC) include Plpp3/Clec4g, Nkg7/Cd3g, C1qa/C1qc, Ebf1/Cd79a, S100a4/Ms4a4, Lsp1/H2afy, Ces1d/Cldn3, Mup3/Car3, Creld2/Fam46c and Dcn/Ecm1, respectively. Next, we used the FindAllMarkers function to find differentially expressed genes between each cell type [8].
Maintaining therapeutic progress in multiple myeloma by integrating genetic and biological advances into the clinic
Published in Expert Review of Hematology, 2018
The loss of 1p32 is associated with adverse outcomes and disease progression. There are a number of sites on 1p that are critical that encompass CDKN2C, FAM46C, and RPL5. HR disease and the deletion or loss of the cyclin dependent kinase inhibitor CDKN2C [71,73,74] deregulates the G1/S cell cycle checkpoint. Another important region of deletion is located at 1p12, which contains FAM46C a gene, which is also frequently mutated.