ASXL1 gene alterations in patients with isolated 20q deletion.

Deletion 20q is a recurrent abnormality in myeloid malignancies. In our previous study, we identified fusion of the additional sex combs-like 1 (ASXL1) and teashirt zinc finger homeobox 2 genes in a patient with myelodysplastic syndrome. The objective of this study was to determine the frequency of ASXL1 breakpoints in a cohort of 36 patients with deletion 20q as the sole cytogenetic aberration. A combination of molecular cytogenetic methods was used to confirm ASXL1 gene alterations in 19 of the 36 patients, and the determination of ASXL1 gene changes in patients with deletion 20q revealed clinical and prognostic impacts.

[Molecular cytogenetic analysis of chromosomal aberrations in cells of low grade gliomas and its contribution for tumour classification]. / Molekulárne cytogenetická analýza chromozomových aberací v bunkách nízkostupnových gliomu a její prínos pro klasifikaci nádoru.

BACKGROUND: Low-grade gliomas represent a heterogeneous group of primary brain malignancies. The current diagnostics of these tumors rely strongly on histological classification. With the development of molecular cytogenetic methods several genetic markers were described, contributing to a better distinction of glial subtypes. The aim of this study was to assess the frequency of acquired chromosomal aberrations in lowgrade gliomas and to search for new genomic changes associated with higher risk of tumor progression. PATIENTS AND METHODS: We analysed biopsy specimens from 41 patients with histological dia-gnosis of low-grade glioma using interphase fluorescence in situ hybridization (I FISH) and single nucleotide polymorphism (SNP) array techniques (19 females and 22 males, medium age 42 years). RESULTS: Besides notorious and most frequent finding of combined deletion of 1p/ 19q (81.25% patients) several other recurrent aberrations were described in patients with oligodendrogliomas: deletions of p and q arms of chromosome 4 (25% patients), deletions of the short arms of chromosome 9 (18.75% patients), deletions of the long arms of chromosome 13 and monosomy of chromosome 18 (18.75% patients). In bio-psy specimens from patients with astrocytomas, we often observed deletion of 1p (24% patients), amplification of the long arms of chromosome 7 (16% patients), deletion of the long arm of chromosome 13 (20% patients), segmental uniparental disomy (UPD) of the short arms of chromosome 17 (60% patients) and deletion of the long arms of chromosome 19 (28% patients). In one patient we detected a shuttered chromosome 10 resulting from chromothripsis. CONCLUSION: Using a combination of I FISH and SNP array, we detected not only known chromosomal changes but also new or less frequent recur-rent aberrations. Their role in cancer  cell progression and their impact on low grade gliomas classification remains to be elucidated in a larger cohort of patients.