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Familial Pancreatic Cancer
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
FPC, in particular familial PDAC, appears to share the same driver mutations in the oncogene KRAS and tumor suppressor genes CDKN2A, TP53, and SMAD4, which are detected in <20% of FPC samples, but in a much higher proportion of pancreatic cancer samples. A number of other genes (e.g., MLL3, TGFBR2, ARID1A, SF3B1, EPC1, ARID2, ZIM2, MAP2K4, NALCN, SLC16A4, MAGE/A6, RNF43, GNAS, RREB1, and PBRM1) may be also implicated in the development of pancreatic cancer [5,8–11].
Precision medicine in ovarian carcinoma
Published in Debmalya Barh, Precision Medicine in Cancers and Non-Communicable Diseases, 2018
Shailendra Dwivedi, Purvi Purohit, Radhieka Misra, Jeewan Ram Vishnoi, Apul Goel, Puneet Pareek, Sanjay Khattri, Praveen Sharma, Sanjeev Misra, Kamlesh Kumar Pant
Recently a study reported 11,479 somatic mutations in the 142 fresh TCGA cases. These mutations were manually reviewed, resulting in a total of 27,280 mutations in 429 cases. TP53, NF1, RB1, CDK12(CRKRS), and BRCA14, as well as the novel SMG, KRAS. BRCA2 and RB1CC1 were reported significantly associated. This group also identified 4 NRAS mutations; 3 NF2 mutations; and 3, 8, and 10 mutations in the identified tumor suppressor genes: ATR, ATM, and APC, respectively. Somatic truncation mutations were also detected in histone modifier genes including ARID1A, ARID1B, ARID2, SETD2, SETD4, SETD6, JARID1C, MLL, MLL2, and MLL3 as well as the DNA excision repair gene ERCC6 (Kanchi et al., 2014). Tables 8.1 and 8.2 have shown the various mutations as characterized by various researchers.
Melanoma
Published in Dongyou Liu, Tumors and Cancers, 2017
Immunohistochemically, melanoma is positive for S100 (nuclear and cytoplasmic staining, 90%+ sensitive but not specific), HMB45 (cytoplasmic and weak nuclear staining, negative in desmoplastic melanoma), MelanA/Mart1 (also stains steroid-producing cells in the ovary, testis, and adrenal cortex), tyrosinase (also stains peripheral nerve sheath and neuroendocrine tumors), microphthalmia transcription factor (MITF) (also stains dermatofibroma and smooth muscle tumors; negative in spindle cell or desmoplastic melanoma), NKI-C3 and NSE (nonspecific), PHH3 and Ki-67 (may distinguish melanoma from nevi), Fontana–Masson (detects melanin granules), vimentin, Cam 5.2, CEA, EMA, α-1-antichymotrypsin, and CD68. Molecularly, melanoma often harbors genetic mutations (ARID2, BAP1, BRAF, GNAQ, HRAS, KIT, NF1, NRAS, and PTEN) and altered pathways (RAS-RAF-MEK-ERK, p16[INK4A]-CDK4-RB, and ARF-p53) [4].
Arid2-IR downregulates miR-132-3p through methylation to promote LPS-induced ALI in pneumonia
Published in Inhalation Toxicology, 2022
Yuanshui Liu, Chuanyu Bao, Gongping Deng, Yanhong Ouyang
Previous studies characterized Arid2-IR as a novel target to improve renal injury (Zhou et al. 2015). In renal inflammation mediated by NF-κB, Arid2-IR targets the transcription of NLRC5 to increase inflammation, thereby promoting renal injury (Zhang et al. 2021). To date, the role of Arid2-IR in other human diseases is unknown. We in this study observed increased expression levels of Arid2-IR in pneumonia. In addition, overexpression of Arid2-IR decreased the viability of HBEpCs under LPS treatment. Therefore, overexpression of Arid2-IR may contribute to pneumonia by decreasing cell viability. In view of the fact that LPS treatment increased the expression levels of Arid2-IR in HBEpCs, we hypothesized that increased LPS in pneumonia patients is a cause of increased expression levels of Arid2-IR. However, animal models are needed to further confirm our conclusion.
Combined endocrine and targeted therapy in luminal breast cancer
Published in Expert Review of Anticancer Therapy, 2021
Marcelle Goldner, Natasha Pandolfi, Debora Maciel, Julianne Lima, Solange Sanches, Noam Pondé
Genetic mechanisms of breast tumorigenesis also encompass transcription regulators (TR). It was found that mutations in MYC, FOXA1, and TBX3 genes were frequent in endocrine-resistant tumors[24]. When heterodimerized with Max, MYC is responsible for stimulating cell proliferation, survival and metabolism, by competing with MAD-MAX repressors of gene promoters. In breast cancer, MYC is stabilized by MAPK and PIK3 cascade members. FOXA1 is a key regulator of ER expression, but its loss is associated with more aggressive behavior (basal-like), which makes this a dubious target [37]. The knockout of encoding members of the SWI/SNF chromatin remodeling complex, ARID1A and ARID2, reduces the expression of transcription factors responsible for luminal identity, such as FOXA1 and GATA3, conferring resistance to endocrine therapy [38]. Considering that bromodomain and extra-terminal (BET) proteins are associated with transcription and recruitment of most of these TR, they are the main targets when these molecules are in focus [39].
Remodeling the cancer epigenome: mutations in the SWI/SNF complex offer new therapeutic opportunities
Published in Expert Review of Anticancer Therapy, 2019
Krystal A Orlando, Vinh Nguyen, Jesse R Raab, Tara Walhart, Bernard E Weissman
The SWI/SNF complex, first discovered in S. cerevisiae, is an evolutionarily conserved multi-subunit complex that utilizes the energy of ATP hydrolysis to mobilize nucleosomes and remodel chromatin [2–6]. Because the complex consists of 12–15 subunits, multiple complex configurations can appear, dependent upon the subunit composition (Figure 1). All complexes include a catalytic ATPase subunit (mutually exclusive SMARCA4/BRG1 or SMARCA2/BRM) and core subunits including BAF155 and SMARCB1 [7]. Separately, three broad sub-families of SWI/SNF complexes have been identified, BAF (BRG1 associated factors), PBAF (Polybromo-associated BAF) and the recently described ncBAF, each defined by signature subunits including ARID1A or ARID1B (BAF), PBRM1 and ARID2 (PBAF), and GLTSCR1 (ncBAF) [8–10]. SWI/SNF complex subfamilies also contain variant subunits, often encoded by multi-gene families. Multiple reports have shown roles for the complex in the regulation of a broad range of normal functions such as gene transcription, RNA processing, cell cycle, apoptosis, development, differentiation, and DNA replication and repair [1]. Thus, with its pivotal role in regulating these diverse pathways, one would predict an association of altered SWI/SNF function with disease.