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Non-Hodgkin Lymphoma
Published in Tariq I. Mughal, Precision Haematological Cancer Medicine, 2018
Waldenström’s macroglobulinemia (WM) has a key driver mutation, MYD88L265P, in >95% of the patients; other important mutations are CXCR4 (40%), ARID1A (17%) and CD79B (15%). Copy number alterations (CNAs) resulting in gene losses occur in PRDM2 (93%), BTG1 (87%), HIVEP2 (77%), MLKN1 (77%), PLEKHG1 (70%), LYN (60%), ARID1B (50%) and FOXP1 (37%). The most common cytogenetic deletions are in chromosome 6q, which mostly overlaps with the CNAs, and comprise of losses in PLEKHG1, HIVEP2, ARID1B and BCLAF1. Mutations in MYD88, which is associated with Toll-like receptor (TLR) and interleukin-1 receptor signalling, mediating IRAK1 and IRAK4, is involved in the NFĸB signalling by direct interaction with BTK.
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.
Medulloblastoma
Published in Dongyou Liu, Tumors and Cancers, 2017
Across all medulloblastoma subsets, frequent genetic alterations relate to chromatin regulators (e.g., MLL2, MLL3, and EHMT1; KDM6A, KDM6B, JMJD2C, and JMJD2B; and SMARCA4, CHD7, and ARID1B) and methylation patterns at and downstream of promoters (e.g., hypomethylation and overexpresssion of the mRNA processing gene LIN28B in most Group 3 and Group 4 tumors [2].
Acute myeloid leukemia with NUP98::RARG resembling acute promyelocytic leukemia accompanying ARID1B gene mutation
Published in Hematology, 2023
All patients who underwent second-generation sequencing harbored a WT1 mutation that may play a role in treatment resistance. Owing to the small number of patients, the impact of the high frequency of WT1 mutations should be investigated in larger and more diverse cohorts in the future. In our patient, SPEN mutation and ARID1B mutation were first reported in this type of patient. ARID1B mutations have been associated with a poor prognosis. Prior studies have reported that silencing ARID1B in the APL cell line NB4 leads to impaired differentiation in response to ATRA. Furthermore, another previous study showed a higher incidence of ARID1B mutations in APL than in non-M3 AML[7]. Therefore, more attention needs to be paid to gene mutations in AML with NUP98::RARG rearrangements, to determine whether the disease has a similar mutational spectrum to APL or non-M3 AML. SPEN gene mutation is common in mature B-cell lymphomas such as diffuse large B-cell lymphoma; however, whether the mutations are involved in the presence of phenotypical APL remains to be elucidated. All patients who received ATRA + ATO induction therapy (≥7 days) showed ATRA and ATO resistance, and subsequently received AML-like induction therapy.
Targeting epigenetic regulators in the treatment of T-cell lymphoma
Published in Expert Review of Hematology, 2020
A number of genes mutated in T-cell lymphomas are involved in histone modifications and chromatin remodeling. KMT2D and KMT2A encode H3K4 methyltransferases, KDM6A encodes an H3K27 demethylase, and SETD2 encodes an H3K36 methyltransferase and also recruits DNMT3B. EP300 and CREBBP encode H3K18 acetyltransferases. Mutations in one of these 6 genes have been identified in 36% of peripheral T-cell lymphoma, not otherwise specified [46]. KMT2D is one of the most commonly mutated genes across all T-cell lymphomas [47], while SETD2 mutations are seen particularly in enteropathy-associated T-cell lymphomas [48,49]. ARID1A and its paralog ARID1B encode AT-rich DNA interacting domain-containing proteins that are components of the SWI/SNF chromatin remodeling complex and have been characterized as tumor suppressors [50]. Loss of function mutations have been identified across a variety of T-cell lymphomas [51–53].
Advances in precision epigenetic treatment for acute promyelocytic leukemia.
Published in Expert Review of Precision Medicine and Drug Development, 2019
Rani Pallavi, Luca Mazzarella, Pier Giuseppe Pelicci
Apart from aberrant DNA or histone acetylation mark, mutations in epigenetic modifier genes (EMG) can also affect clinical outcome. Indeed, mutations of DNMT3A, TET2, IDH1, IDH2 and ASXL1 as a group were associated with poor response to ATRA/ATO therapy and poor prognosis in terms of DFS [97]. Moreover, a comprehensive mutational analysis of APL, at both initial diagnosis and relapse, uncovered recurrent mutations in ARID1A and ARID1B genes, members of SWI/SNF complex. Frequently identified at relapse, mutations of ARID1B impairing the activity of key components of the SWI/SNF complex were consistent with the variability in the response to ATRA treatment in ARID1B deficient NB4 cells [98], suggesting that screening for the presence of EMG mutations in patients at diagnosis might predict resistance to ATRA/ATO treatment.