Genome‐wide studies in tumor cells have indicated that chromatin‐modifying proteins are commonly mutated in human cancers. The lysine‐specific methyltransferase 2C ( KMT 2C/ MLL 3) is a putative tumor suppressor in several epithelia and in myeloid cells. Here, we show that downregulation of KMT 2C in bladder cancer cells leads to extensive changes in the epigenetic status and the expression of DNA damage response and DNA repair genes. More specifically, cells with low KMT 2C activity are deficient in homologous recombination‐mediated double‐strand break DNA repair. Consequently, these cells suffer from substantially higher endogenous DNA damage and genomic instability. Finally, these cells seem to rely heavily on PARP 1/2 for DNA repair, and treatment with the PARP 1/2 inhibitor olaparib leads to synthetic lethality, suggesting that cancer cells with low KMT 2C expression are attractive targets for therapies with PARP 1/2 inhibitors.

Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease accounting for 15–20% of all childhood acute leukemias, while it is responsible for more than half of the leukemic deaths in these patients. This article focuses on the significance of cytogenetic analysis in pediatric AML supporting the importance of cytogenetic analysis in the pathogenesis, diagnosis, prognosis, follow‐up and treatment selection in childhood AML. It reviews in detail the types and frequencies of most common chromosomal aberrations, their molecular background, their correlation with French American British (FAB) subtypes and age distribution and their prognostic relevance. It also summarizes some less frequent or rare chromosome aberrations in which the prognostic classification has not been determined yet owning to the small number of patients and the variable treatment modalities used in different study groups. Furthermore, it discusses the association of specific chromosome rearrangements with prenatal exposure to carcinogenic agents or therapeutic agents and highlights the ongoing and future research on pediatric AML in the evolving field of Cytogenetics.

Summary Acute leukaemia of ambiguous lineage (ALAL) is a rare complex entity with heterogeneous clinical, immunophenotypic, cytogenetic and molecular genetic features and adverse outcome. According to World Health Organization 2008 classification, ALAL encompasses those leukaemias that show no clear evidence of differentiation along a single lineage. The rarity of ALAL and the lack of uniform diagnostic criteria have made it difficult to establish its cytogenetic features, although cytogenetic analysis reveals clonal chromosomal abnormalities in 59–91% of patients. This article focuses on the significance of cytogenetic analysis in ALAL supporting the importance of cytogenetic analysis in the pathogenesis, diagnosis, prognosis, follow up and treatment selection of ALAL. It reviews in detail the types of chromosomal aberrations, their molecular background, their correlation with immunophenotype and age distribution and their prognostic relevance. It also summarizes some novel chromosome aberrations that have been observed only once. Furthermore, it highlights the ongoing and future research on ALAL in the field of cytogenetics.

Mutations of ASXL1 are early events in acute myeloid leukemia (AML) leukemogenesis and have been associated with unfavorable prognosis. In this study, we investigated the type and frequency of ASXL1 mutations in a large cohort of patients with de novo or secondary AML (s-AML) and looked for correlations with cytogenetic findings and disease features. ASXL1 mutations were associated with older age, s-AML and higher peripheral leukocytosis. We observed more frequent co-occurrence of ASXL1 mutations with trisomy 8 and chromosome 11 aberrations but a negative correlation with myelodysplastic syndromes (MDS)-related cytogenetic abnormalities, especially -5/del(5q) and -7/del(7q). ASXL1 mutations were also found in other genetically defined AML subgroups such as those with t(9;22), inv(3)/t(3;3), t(8;21) or t(15;17); however, none of our inv(16) cases carried ASXL1 mutations. We detected two previously unreported ASXL1 mutations, p.IIe593Val and p.Cys688Tyr. Our findings suggest that ASXL1 mutations tend to cluster with specific clinical and cytogenetic profiles of AML patients.

Isochromosome of the long arm of the derivative chromosome 17, originating from the translocation t(15;17) [ider(17)(q10)t(15;17) or ider(17q)] in acute promyelocytic leukemia (APL), is a rare chromosome aberration which has been associated with a poor prognosis. In the present study, we report on 4 male APL patients with ider(17q) and review the clinical, cytogenetic and molecular characteristics of all previously reported APL patients with ider(17q) in order to clarify the clinical features and outcome of these patients. The data presented in this study demonstrated that ider(17q), which resulted in an extra RARA-PML fusion gene, was more frequent in males than females (male/female ratio of 2.12/1), was associated with a rather low initial white blood cell count and did not confer an adverse prognosis in APL patients treated with all-trans-retinoic acid and chemotherapy. The most frequent additional chromosome change to ider(17q) was trisomy 8. Ider(17q) was observed in all subtypes of the PML-RARA fusion gene, but the frequency of the bcr1 subtype was increased. Cases of overrepresentation of the RARA-PML fusion gene and ider(17q) cases may help in elucidating the role of RARA-PML in leukemogenesis.

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This study aimed to investigate whether occupational and environmental exposures, lifestyle, family, and medical history are associated with chronic lymphocytic leukemia (CLL) risk and its chromosomal abnormalities. The study included 138 CLL cases and 141 age- and sex-matched controls. Information data were collected through in-person interviews from cases and controls. Cytogenetic analysis was performed on CLL bone marrow cells. Positive associations were found between CLL and cancer family history, smoking, pneumonia, and exposure to petroleum, metals, pesticides/chemical fertilizers, detergents, and medical radiation. Chromosome deletions of 11q and 13q were more frequent in patients exposed to pesticides and rubber, respectively. This study investigated for the first time specific risk factors in relation to CLL aberrations and presented positive correlations. Moreover, it indicates the possible involvement of specific occupational and lifestyle risk factors in the onset of CLL.

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