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PubMed2007

Rearrangement rate following the whole-genome duplication in teleosts.

It is now clear that a whole-genome duplication (WGD) occurred at the base of the teleost fish lineage. Like the other anciently polyploid genomes investigated so far, teleost genomes now behave like diploids with chromosomes forming pairs at meiosis. The diploidization process is currently poorly understood. It is associated with many gene deletions, such that one of the duplicates is lost at most loci and has also been proposed to coincide with an increase in genomic instability. Here we ask whether WGD is a determinant of the genomic rearrangement rate in teleosts. We study variability of the rates of rearrangement along a vertebrate phylogenetic tree, composed of 3 tetrapods (human, chicken, and mouse) and 3 teleost fishes (zebrafish, Tetraodon, and Takifugu), whose complete genome sequences are available. We devise a simple parsimony method for counting rearrangements, which takes into account various methodological complications caused by the WGD and the subsequent gene losses. We show that there does appear to be an increase in rearrangement rate after WGD, but that there is also a great deal of additional variability in rearrangement rates across species.

Animals↗
PubMed1998

Prevalence of minisatellite and microsatellite instability in radiation-induced post-Chernobyl pediatric thyroid carcinomas.

Exposure to ionizing radiation induces different forms of genomic instability in cultured cells and experimental animals. A higher rate of germline mutations at human hypervariable minisatellite loci was reported in children born from parents exposed to radiation after Chernobyl, implicating genome destabilization as a possible mechanism responsible for late radiation effects in humans. To test if radiation-induced carcinogenesis in the thyroid gland may be associated with somatic minisatellite instability or microsatellite instability, we utilized a PCR-based approach to study normal and tumor DNA from 17 pediatric post-Chernobyl papillary thyroid carcinomas for mutations at three different minisatellite loci (D1S80, D17S30, ApoB), and 27 microsatellite loci of di-, tri-, or tetranucleotide repeats. Minisatellite instability was found in three (18%) tumors, with one of them exhibiting mutations in all three minisatellite loci, whereas two others showed mutations in one of two informative markers. By contrast, none of 20 sporadic thyroid cancers from patients with no history of radiation exposure was positive for minisatellite instability. Microsatellite analysis of post-Chernobyl tumors revealed a mutation in one (6%) tumor only at the locus of D10S1412, whereas all other 26 microsatellite markers showed identical patterns in each normal/tumor pair. Our results suggest that somatic cell microsatellite instability does not contribute to radiation-induced thyroid carcinogenesis. However, somatic minisatellite mutation events are present in a subset of radiation-induced, but not sporadic, thyroid cancers, suggesting that this type of genomic instability may play a role in radiation-induced tumorigenesis in the thyroid gland.

Adolescent↗
PubMed1995

Microsatellite instability and pathological aspects of breast cancer.

Genomic instability plays a key role in hereditary nonpolyposis colorectal cancer and in a significant sub-set of non-hereditary colorectal tumors. Recent evidence suggests that microsatellite instability also occurs in various sub-sets of common, non-hereditary forms of extra-colorectal carcinoma. To investigate the role of microsatellite instability in breast cancer, and to correlate this type of alteration with clinico-pathological characteristics, including tumor proliferative activity, we analyzed the status of 8 different microsatellite loci in 28 cases of primary mammary carcinoma. For this purpose, microsatellite banding patterns were compared in paired breast-cancer/peripheral-blood DNA samples. Microsatellite instability was observed in 6/28 (21%) of the cases. Four of the 6 tumors had low proliferative activity, one had high proliferative activity, and in one case proliferative activity values were not available. All chromosomal loci investigated demonstrated microsatellite instability in one or more representative tumors of the series. Shifts in length larger than 2 bp were the most frequent change. Microsatellite instability significantly correlated with the lobular histotype, and with lymph-node involvement. A trend was also observed associating microsatellite instability and large tumor size.

Adult↗
PubMed1999

Frequent aberration of the transforming growth factor-beta receptor II gene in cell lines but no apparent mutation in pre-invasive and invasive carcinomas of the uterine cervix.

The type II transforming growth factor-beta (TGF-beta) receptor (RII) gene located at 3p22 plays an important role in regulating growth and differentiation of epithelium, including that of the uterine cervix. Loss-of-function mutations of RII have frequently been found in gastrointestinal cancers, with a replication-error (RER) phenotype characterized by the presence of microsatellite instability (MI). In this study, genomic PCR, SSCP and DNA sequencing were conducted to investigate the coding sequences of the RII gene in cell lines (n = 5) and tissues (n = 15) of squamous carcinomas of the uterine cervix. Intragenic deletions were noted in 2 of 5 cervical-cancer cell lines (ME180 and HeLa cells). However, no mutation, other than DNA polymorphisms, was found in 15 cervical cancers with either alleleic loss at 3p22 (n = 11) or MI (n = 4). Further analysis of squamous intraepithelial lesions (SIL) with (n = 12) or without (n = 4) MI for the (A)10 change, a prototypic mutation found in over 90% of RER-positive colon cancers, also showed no aberration. Our study concludes that the RII gene is frequently disrupted in cervical-cancer cell lines, but is rarely mutated in CC and SIL tissues, including those showing MI or alleleic loss at 3p22. The underlined mechanism of genomic instability in CC and SIL may thus differ from that of colorectal cancer. The allelic loss at 3p22-24 in CC does not involve the coding sequence of the RII gene. The non-coding sequence of RII or an unidentified gene may be responsible for it.

Carcinoma, Squamous Cell↗
PubMed1986

Biology of metastasis.

The acquisition by tumor cells of the ability to metastasize is the critical event in the clinical course of most human neoplastic disease. While metastasis plays a pivotal role in the ultimate success of failure of therapy, it is in fact a result of a more insidious malignant process termed tumor progression. It is the progression of tumors from a less to a more malignant phenotype that results in tumor heterogeneity and the selection of cells with a more malignant (metastatic) phenotype. The development of metastases is thus integrally related to the mechanisms of tumor progression, which in turn is likely due to the instability of the tumor cell genome. The authors' thesis is that metastatic tumor cells are a selected population derived from a heterogeneous parent tumor which contains many clones with different phenotypes. This discussion will, therefore, address the role of tumor genomic instability as a basis for the selection of metastatic cells.

Animals↗
PubMed2026

Stratifying lung adenocarcinoma: a novel prognostic model based on mitochondrial outer membrane permeabilization activity.

UNLABELLED: Mitochondrial outer membrane permeabilization (MOMP) is a core apoptotic regulatory event that dictates mitochondrial integrity, where full activation drives cell death and sublethal dysregulation contributes to tumor genomic instability. We used the Cancer Genome Atlas lung adenocarcinoma cohort (TCGA-LUAD) as the training cohort and the Gene Expression Omnibus dataset GSE42127 as the validation cohort to identify prognostic genes related to MOMP activity in lung adenocarcinoma (LUAD) and to evaluate their potential biological significance. By intersecting MOMP-related genes with differentially expressed genes, combined with survival analysis, Mendelian randomization analysis, and 101 machine-learning algorithm combinations, seven prognostic genes, namely BIRC5, PSMD11, TNFRSF13C, YWHAZ, YWHAG, CYCS, and LTB, were identified. Next, an optimal prognostic model was constructed based on the gradient boosting machine (GBM) algorithm. Based on the risk score, LUAD patients were stratified into high- and low-risk groups, and patients in the high-risk group exhibited poorer overall survival in both the training and validation cohorts. Furthermore, a nomogram integrating the risk score and clinicopathological factors was developed and showed favorable predictive performance for 1-, 3-, and 5-year survival. Meanwhile, functional and immune analyses revealed that the high-risk group was enriched in DNA replication-related pathways and demonstrated a higher tumor mutation burden (TMB). Correlation analysis indicated that TNFRSF13C was positively correlated with activated B cells, whereas BIRC5 was negatively correlated with eosinophils, suggesting that MOMP-related genes might be involved in remodeling the immune microenvironment of LUAD. Drug sensitivity analysis showed differences in predicted half-maximal inhibitory concentration (IC50) values between the risk groups, suggesting the potential value of this model in assisting therapeutic stratification. Single-cell RNA sequencing (scRNA-seq) further identified T lymphocytes as a key cell type, with numerous prognostic genes exhibiting differential expression in T cells or dynamic changes during differentiation. We suggest that the MOMP-related signature established in this study may provide a reference for prognostic stratification in LUAD and offers candidate prognostic genes for subsequent experimental and clinical validation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at https://doi.org/10.1007/s13205-026-05058-6.

Lung adenocarcinoma↗
PubMed1998

Analysis of the frequency of microsatellite instability and p53 gene mutation in splenic marginal zone and MALT lymphomas.

AIMS: Studies of the genetic characteristics of splenic marginal zone lymphoma (SMZL) have failed to identify genetic changes specific to this tumour. Microsatellite instability is a type of genomic instability associated with different types of human cancer. Although microsatellite instability is rare in B cell non-Hodgkin's lymphomas, it has been found in some specific subsets, such as marginal zone lymphomas arising in mucosa associated lymphoid tissue (MALT), where an association with p53 mutation has been described. Because it has been proposed that SMZL and MALT are close in histogenetic terms, this study investigated the comparative frequency of microsatellite instability and p53 mutation in patients with SMZL and MALT lymphomas. METHODS: Microsatellite instability was investigated using seven microsatellite marker loci in 14 patients with SMZL and 20 patients with MALT lymphomas. In an attempt to clarify the role of p53 gene mutation in the pathogenesis of SMZL, exons 5-8 were also investigated by polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) and direct sequencing in a total of 20 patients with SMZL and 22 patients with MALT lymphomas. RESULTS: Microsatellite instability was not detected in patients with SMZL, although five of 20 patients with MALT lymphomas had microsatellite instability. The frequency of p53 mutation was low in both series (two of 20 patients with SMZL and one of 22 patients with MALT lymphomas). No significant association was found between p53 mutation and microsatellite instability. CONCLUSIONS: These results indicate that microsatellite instability is not associated with the molecular pathogenesis of SMZL, confirming the relatively increased frequency of microsatellite instability in MALT lymphomas, and perhaps suggesting that MALT and SMZL have different mechanisms of tumorigenesis.

Genes, p53↗
PubMed2006

MYC can enforce cell cycle transit from G1 to S and G2 to S, but not mitotic cellular division, independent of p27-mediated inihibition of cyclin E/CDK2.

Overexpression of the MYC proto-oncogene exerts protean biological effects that may contribute to its ability to induce tumorigenesis including enforcing cellular growth and proliferation and inducing genomic instability. MYC overexpression may induce genomic damage at least in part by causing inappropriate DNA replication. MYC may induce inappropriate DNA replication through the activation of Cyclin E/CDK2. To address this possibility, the effects of ectopic p27 expression in immortal rat fibroblasts or human breast epithelial cell lines on MYC-induced endo-reduplication was determined. p27 inhibited Cyclin E/CDK2 associated kinase activity, but failed to prevent MYC from inducing transit from G1 to S phase; inhibited at lower but not higher levels of MYC transit from G2 to S and endo-reduplication; however, MYC failed to enforce mitotic cellular division. In addition, MYC was found to induce Cyclin E; and Cyclin E in turn was found to be able to induce endo-reduplication. Hence, MYC appears induce inappropriate cell cycle transit, but not mitotic cellular division independent of p27 mediated inhibition of Cyclin E/Cdk2. Our results have implications for the mechanisms by which MYC overexpression dysregulates cell cycle transit, causes genomic destabilization and is restrained from causing tumorigenesis.

Animals↗
PubMed2026

In vitro fertilization-conceived offspring exhibit altered Long Interspersed Nuclear Elements-1 retrotransposition dynamics associated with long-term disease risks.

BACKGROUND: In vitro fertilization has transformed reproductive medicine, yet offspring conceived through in vitro fertilization display elevated risks for diverse long-term health conditions, with underlying mechanisms unclear. Long Interspersed Nuclear Elements-1, a mobile genetic element responsive to environmental stress, represents a potential mediator. OBJECTIVE: This study aimed to test the hypothesis that in vitro fertilization procedures may act as an embryonic stressor that alters Long Interspersed Nuclear Elements-1 dynamics, potentially contributing to genomic instability associated with long-term disease susceptibility. STUDY DESIGN: Umbilical cord blood or peripheral blood from 33 in vitro fertilization and 42 naturally conceived neonates were collected for whole-genome sequencing. Total Long Interspersed Nuclear Elements-1 proportion in individual genome was counted with Bowtie2 software. De novo Long Interspersed Nuclear Elements-1 insertion and Long Interspersed Nuclear Elements-1 deletion were detected with Mobile Element Locator Tool. Three parent-matched in vitro fertilization-naturally conceived sibling pairs were included to control for genetic background. Disease association analysis was performed for genes within 500 kb of differential Long Interspersed Nuclear Elements-1 sites in The Database for Annotation, Visualization and Integrated Discovery (DAVID). Statistical analysis was performed using the R language. RESULTS: In vitro fertilization offspring demonstrate elevated global Long Interspersed Nuclear Elements-1 content compared to naturally conceived controls (P=.04). This finding was corroborated in 3 sibling pairs from identical genetic backgrounds, where in vitro fertilization-conceived children consistently exhibited higher Long Interspersed Nuclear Elements-1 levels than their naturally conceived siblings. Eleven genomic loci with differential Long Interspersed Nuclear Elements-1 insertion frequencies and 14 loci with differential Long Interspersed Nuclear Elements-1 deletion frequencies between in vitro fertilization offspring and naturally conceived controls were identified. Notably, these differential Long Interspersed Nuclear Elements-1 sites demonstrated significant enrichment near genes implicated in metabolic, cardiovascular, neuropsychiatric, and neoplastic diseases, conditions associated with in vitro fertilization conception. CONCLUSION: These findings provide preliminary evidence that in vitro fertilization conception is associated with increased Long Interspersed Nuclear Elements-1 content and altered genomic distribution of Long Interspersed Nuclear Elements-1 elements. The proximity of these differential Long Interspersed Nuclear Elements-1 sites to disease-associated genes suggests a plausible genomic mechanism linking in vitro fertilization-associated embryonic stress to elevated disease risk. This work provides valuable molecular insights that may inform the ongoing discussion about assisted reproductive technology safety and suggests that continued attention to genomic integrity in in vitro fertilization-conceived individuals would be beneficial.

Humans↗
PubMed2006

Mismatch repair protein expression and microsatellite instability: a comparison of clear cell sarcoma of soft parts and metastatic melanoma.

Clear cell sarcoma of soft parts is a rare soft tissue malignancy that shows phenotypic overlap with cutaneous melanoma but can be distinguished by the presence of a t(12;22) translocation. Microsatellite instability (MSI), a variation in the lengths of short repeat DNA segments in the genome, has been implicated in melanoma tumorigenesis, but is rare or absent in clear cell sarcoma. Defects in the mismatch repair (MMR) enzyme complex correlate with MSI in some tumor types, allowing the use of immunohistochemistry for the MMR proteins hMLH1 and hMSH2 to predict the presence of MSI. To determine if the association between MMR defects and MSI extends to clear cell sarcoma, we compared a group of nine clear cell sarcomas to 11 metastatic melanomas on the basis of MSI and the expression of MMR proteins. MSI was studied using fluorescence-based multiplexed PCR of five loci. Immunohistochemistry was evaluated on formalin-fixed paraffin-embedded tissue for hMLH1, hMHS2 and hMSH6. MSI was present in only 1/9 (11%) clear cell sarcoma case and in 8/11 (73%) melanoma cases. Immunostaining for hMLH1 and hMSH2 was preserved in all the clear cell sarcomas but loss of immunostaining for one or both proteins was seen in 6/11 melanomas (55%). hMSH6 was detected in 7/9 (78%) clear cell sarcomas and 10/11 (91%) of melanomas. Clear cell sarcoma and metastatic melanoma differed significantly with respect to the presence of MSI (P=0.010) and staining for hMLH1 and/or hMSH2 (P=0.014) but not hMSH6 (P=0.57). Mismatch repair, and consequently genomic instability may contribute to tumorigenesis in melanoma but not clear cell sarcoma. Immunostaining for hMLH1 and hMSH2 and MSI analysis may be helpful in the differential diagnosis of large soft tissue or visceral malignancies with melanocytic differentiation.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Somatic evolution of cancer cells.

Cancers develop through a process called genomic instability, which generates diversity, from which clonal evolution may occur. In colorectal cancers, this process has been extensively studied, and there are three identifiable processes involved in generating diversity at the genetic or epigenetic level. Colorectal cancers may have chromosomal instability (CIN), microsatellite instability (MSI), or the CpG island methylator phenotype (CIMP). Each of these processes is associated with a unique mutational or epigenetic "signature" identifiable in the tumor cells, and there are important conceptual and clinical implications of each.

Adenoma↗
PubMed2026

Somatic mutations and genome mosaicism in aging and disease.

Age-related genome mosaicism is an inherent feature of multicellularity and genomic instability. It occurs because of DNA mutations, the accumulation of which leads to diverse genomic landscapes across different tissues. DNA mutations in the genome are consequences of DNA damage, changes in the chemical structure of DNA, such as strand breaks or loss of bases. DNA damage is very frequent and normally repaired quickly. However, errors intrinsic to DNA repair or replication can give rise to permanent changes in genome sequence information. Such DNA mutations are diverse and include single-nucleotide variants, small insertions and deletions, and larger genome structural variants. Since the 1950s, somatic mutations have been proposed to be a major cause of aging. Indeed, somatic mutations are the cause of cancer, the risk of which increases exponentially with age, and possibly other age-related diseases, such as neurodegenerative diseases and cardiomyopathies. Somatic mutations vary from cell to cell owing to the innate stochasticity of their occurrence, from error-prone processing of randomly inflicted DNA damage. With the emergence of single-cell and single-molecule sequencing, it has become possible to quantitatively analyze somatic mutations in human cells and tissues. Here, we discuss a possible causal relationship between mutation-driven mosaicism of the somatic genome and aging-related functional decline and disease by exploring several predictions of the somatic mutation theory of aging.

Humans↗
PubMed2004

A functional analysis reveals dependence on the anaphase-promoting complex for prolonged life span in yeast.

Defects in anaphase-promoting complex (APC) activity, which regulates mitotic progression and chromatin assembly, results in genomic instability, a hallmark of premature aging and cancer. We investigated whether APC-dependent genomic stability affects aging and life span in yeast. Utilizing replicative and chronological aging assays, the APC was shown to promote longevity. Multicopy expression of genes encoding Snf1p (MIG1) and PKA (PDE2) aging-pathway components suppressed apc5CA phenotypes, suggesting their involvement in APC-dependent longevity. While it is known that PKA inhibits APC activity and reduces life span, a link between the Snf1p-inhibited Mig1p transcriptional modulator and the APC is novel. Our mutant analysis supports a model in which Snf1p promotes extended life span by inhibiting the negative influence of Mig1p on the APC. Consistent with this, we found that increased MIG1 expression reduced replicative life span, whereas mig1Delta mutations suppressed the apc5CA chronological aging defect. Furthermore, Mig1p and Mig2p activate APC gene transcription, particularly on glycerol, and mig2Delta, but not mig1Delta, confers a prolonged replicative life span in both APC5 and acp5CA cells. However, glucose repression of APC genes was Mig1p and Mig2p independent, indicating the presence of an uncharacterized factor. Therefore, we propose that APC-dependent genomic stability is linked to prolonged longevity by the antagonistic regulation of the PKA and Snf1p pathways.

Aging↗
PubMed2026

Acute Myeloid Leukemia With KMT2A Amplification: A TP53-Alteration-Enriched Subgroup Associated With Chromoanagenesis and Poor Prognosis.

KMT2A amplification (KMT2A-amp) is a rare but aggressive genomic abnormality in acute myeloid leukemia (AML), with limited characterization in prior studies. We retrospectively analyzed 96 patients with AML harboring KMT2A-amp, including 56 newly diagnosed (ND) and 40 relapsed/refractory (RR) cases, with a median age of 68 years. Approximately half of the cases had therapy-related or secondary AML. All cases demonstrated highly complex karyotypes, with frequent -5/del(5q), -7/del(7q), and -17/del(17p). TP53 alteration was present in 93% of patients, whereas other recurrent AML-associated mutations were uncommon, and no AML-defining gene fusions or mutations were identified. In cases evaluated by optical genome mapping, all showed chromoanagenesis involving chromosome 11q23 region. Clinical outcomes were poor, with a median overall survival of 5.5 months in ND and 2.3 months in RR patients. Intensive chemotherapy did not improve survival compared with lower-intensity therapy, whereas venetoclax-based regimens were associated with improved overall survival (7.1 vs 4.6 months; p = 0.04) and event-free survival (6.7 vs 0.17 months; p < 0.01). We conclude that KMT2A-amp AML represents an extremely high-risk subgroup occurring in the context of TP53-associated genomic instability and chromoanagenesis. Its refractoriness to conventional chemotherapy highlights the urgent need for more effective, targeted therapeutic strategies.

KMT2A amplification↗
PubMed1995

Genomic alterations and instabilities in renal cell carcinomas and their relationship to tumor pathology.

A comprehensive genome scan for loss of heterozygosity (LOH) in 33 renal cell carcinomas indicates that mutations of tumor suppressor genes on several different chromosomes are required for malignant transformation in this disease. In the case of nonpapillary renal carcinomas chromosomes 3p, 6q, 8p, 9pq, and 14q exhibit elevated levels of LOH. Although 3p is the most frequently lost chromosome arm, in no case is 3p observed as the sole allelic loss because it always occurs in conjunction with the loss of either 6q, 8p, or 14q. This result indicates that the mutation of a tumor suppressor gene on 3p, most likely von Hippel-Lindau disease (VHL), may be necessary but is not sufficient for the development of nonpapillary renal cell carcinoma. In papillary renal tumors, LOH is observed most often for chromosomes 6pq, 9p, 11q, 14q, and 21q. This suggests that tumor suppressor genes located on chromosomes 6q, 9pq, and 14q may be involved in the development and/or progression of both nonpapillary and papillary renal cell carcinomas. However, LOH in papillary tumors appears to be especially elevated for 11q and 21q and reduced for 3p and 8p indicating that there are also tumor suppressor genes specific to each form of the disease. There is no correlation between stage of disease and the extent of LOH, loss of a particular chromosome, or the number of chromosomes that show allele imbalance. Early and late stage tumors may exhibit either extensive LOH or no apparent allele loss; similarly, allelic imbalances are observed in both early and late stage renal cell carcinomas. This suggests that a gene (or genes) regulating mitotic chromosome stability may be mutated in some renal tumors. Preliminary evidence points to an association between genome instability and LOH of 14q. Finally, a distinct type of microsatellite instability has been detected in 21% of renal cell carcinomas and occurs at a frequency of 4.4 x 10(-4)/locus. The most common mutation is a 2-bp insertion in a CA repeat. This alteration is not restricted to a particular histopathology or clinical stage, and it is not associated with allelic loss of a specific chromosome. The frequency of this event is similar to that which occurs spontaneously in germline microsatellite loci and is probably not the result of a defect in a mismatch repair gene. It is possible that this type of microsatellite instability is general and may occur in most, if not all, carcinomas.

Alleles↗
PubMed1990

Common variable immunodeficiency and malignancy: a report of two cases and possible explanation for the association.

Two patients with common variable immunodeficiency (CVID) and malignant tumours are reported. The first patient developed myelogenous leukaemia soon after the myelodysplastic syndrome has been diagnosed. The undifferentiated gastric lymphoma found in the second patient suggests that an increased risk of gastrointestinal malignancies in CVID could partly be due to lymphomas. We hypothesize that the tissue- or site-specific risk of lymphomas and gastrointestinal cancer can be explained by an increased chromosomal or genomic instability with a higher mutation rate and genomic disorganization, and that this instability could be related to viral carcinogenesis. The primary immunodeficiency per se may not be responsible for the cancer susceptibility in CVID patients.

Adult↗
PubMed2006

Genomic alterations in Hodgkin's lymphoma.

Cytogenetic analysis of Hodgkin's lymphoma (HL) is hampered by the scarcity of neoplastic cells within a sea of reactive cells. There is accumulating evidence that HL represents 2 disease entities, classic HL (cHL) with its morphologic variants and nodular lymphocyte predominant HL (NLPHL). This subdivision, initially worked out in morphologic and immunohistochemical studies, has been further substantiated by molecular cytogenetic investigations. Two recurrent chromosomal aberrations, namely gains of 2p13-p16 and 9p24, have been found by comparative genomic hybridization analysis in microdissected cells from cHL patients as well as in cHL cell lines, but not in NLPHL cells. The available cHL cell lines are remarkably heterogeneous in their karyotypes, suggesting profound genomic instability leading to numeric chromosomal aberration and multiple chromosomal breaks and translocations. In this article, we review genomic aberrations that may contribute to the development and maintenance of the morphologic and clinical presentation of these beta-cell lymphoma entities. Furthermore, we delineate current data on the genomic changes observed in the neoplastic cells of HL that are created by epigenetic mechanisms, which are alternative mechanisms that regulate the expression of relevant genes.

Chromosome Aberrations↗
PubMed2003

Hydrolytic nucleoside and nucleotide deamination, and genetic instability: a possible link between RNA-editing enzymes and cancer?

Post-transcriptional RNA editing generates novel gene products by changing the coding sequence of the transcript from that in the genome. Two classes of RNA editing exist in mammals, each of which involves an enzymatic deamination. These reactions have stringent sequence and structural requirements for their target RNAs, and each requires distinctive enzymatic machinery. Alterations in the expression or abundance of RNA-editing factors produce unanticipated alterations in the processing or expression of RNAs, in some cases outside their physiological targets. Recent findings suggest that unregulated expression of the cytidine-deaminase gene family might lead to deamination of deoxycytidine nucleotides in DNA. Aberrant or dysregulated RNA editing, or altered expression of editing factors, might contribute to genomic instability in cancer.

Animals↗