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Multiplex ligációfüggő szondaamplifikáció alkalmazásának lehetőségei onkohematológiai kórképek DNS kópiaszám eltéréseinek vizsgálatában
Get PDFAnalysis of DNA copy number aberrations (CNAs) plays an important role in the
routine diagnostic workup of hematological malignancies. Since these alterations are
frequently of clinical significance there is a need for their fast and cost-efficient detection.
The multiplex ligation-dependent probe amplification (MLPA) is a PCR based method
enabling assessment of CNAs at 50-60 different loci and is also capable of the
simultaneous detection of point mutations. The next generation sequencing based digital
MLPA (dMLPA) can be even more efficient with analyzing the CNA status of 500 to
1000 loci in one run.
In our study, we examined the efficacy of the conventional MLPA in samples
from 18 newly diagnosed and 6 ibrutinib treated CLL patients. We also tested a novel
dMLPA assay developed for MM in bone marrow samples of 56 MM patients.
Additionally, we utilized a dMLPA assay in pediatric ALL for the detection of clinically
relevant aberrations and dissection of mechanisms leading to disease relapse. We paid
special attention to the identification of clinically relevant abnormalities and the
dissection of the genetic alterations leading to relapse.
Using conventional MLPA in CLL, we identified prognostic aberrations in several
cases and we also successfully applied the method to reveal patterns of clonal evolution
induced by ibrutinib treatment. In MM, we were the first in the international literature to
demonstrate the effectiveness dMLPA in detailed analysis of CNAs with prognostic and
predictive value in the disease. In childhood ALL, in addition to mapping clinically
relevant CNAs using dMLPA, three different clonal mechanisms were discovered based
on the CNA profiles in paired diagnostic and relapsed samples. Furthermore, we
introduced a new risk classification system by combining dMLPA-defined CNAs and
cytogenetic abnormalities.
Based on our study, MLPA-based techniques represent useful complementary
approaches to methods used in the routine diagnostic setting and can also be successfully
applied in research of malignant hematological diseases
Chemodiversity between selected Cardueae and Anthriscus plant species: a phytochemical study of their intact tissues and in vitro cultures
Get PDFMORPHOLOGICAL AND FUNCTIONAL CHARACTERIZATION OF THE ATHLETE’S HEART USING ADVANCED ECHOCARDIOGRAPHIC TECHNIQUES
Get PDFMembrane Permeability and Aqueous Stability Study of Linear and Cyclic Diarylheptanoids from Corylus maxima
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FACTORS IN CHILDHOOD AND ADULTHOOD INFLUENCING THE DEVELOPMENT AND TREATMENT OF LOW BACK PAIN
Get PDFGlycogen synthase kinase 3 beta gene structural variants as possible risk factors of bipolar depression
Get PDFThe glycogen synthase kinase 3B (GSK3B) is an important target protein of several antidepressants, such as lithium, a mood stabilizer. Recent studies associated structural variations of the GSK3B gene to bipolar disorder (BP), although replications were not conclusive. Here we present data on copy number variations (CNVs) of the GSK3B gene probing the 9th exon region in 846 individuals (414 controls, 172 patients with major depressive disorder (MDD) and 260 with BP). A significant accumulation (odds ratio: 5.5, P=0.00051) of the amplified exon 9 region was found in patients (22 out of 432) compared to controls (4 of 414). Analyzing patient subgroups, GSK3B structural variants were found to be risk factors of BP particularly (P=0.00001) with an odds ratio of 8.1 while no such effect was shown in the MDD group. The highest odds (19.7 ratio) for bipolar disorder was observed in females with the amplified exon 9 region. A more detailed analysis of the identified GSK3B CNV by a set of probes covering the GSK3B gene and the adjacent NR1I2 and C3orf15 genes showed that the amplified sequences contained 3' (downstream) segments of the GSK3B and NR1I2 genes but none of them involved the C3orf15 gene. Therefore, the copy number variation of the GSK3B gene could be described as a complex set of structural variants involving partial duplications and deletions, simultaneously. In summary, here we confirmed significant association of the GSK3B CNV and bipolar disorder pointing out that the copy number and extension of the CNV varies among individuals. © 2014 Wiley Periodicals, Inc
