ISSN 1866-8836
Клеточная терапия и трансплантация

AL-06. Loss of heterozygosity in the short tandem repeat (STR) profile of tumor DNA of de novo diagnosed ALL patients as a pattern of abnormal karyotype

Natalya V. Risinskaya1, Yana A. Kozhevnikova2, Valeriya A. Kovaleva2, Olga A. Gavrilina1, Julia A. Chabaeva1, Anna A. Yushkova1, Natalia S. Kostritsa2, Sergei M. Kulikov1, Elena N. Parovichnikova1, Andrey B. Sudarikov1

1 National Research Center for Hematology, Moscow, Russia
2 School of Medicine, Lomonosov Moscow State University, Moscow, Russia

Contact: Dr. Natalya V. Risinskaya, e-mail:

doi 10.18620/ctt-1866-8836-2020-9-3-1-152



Genetic instability of tumor cells can lead to a change in the profile of short tandem repeats (STR) of the tumor relative to the STR profile of healthy cells of the patient. Loss of heterozygosity or allelic imbalance in STR loci confirm the chromosomal aberrations revealed by standard cytogenetic analysis in chromosomes containing this STR locus: deletions, monosomies, duplications, and the appearance of isochromosomes. However, in some patients, the loss of heterozygosity is also observed with a normal tumor karyotype. Our objective was to evaluate correlations between the loss of heterozygosity in blast cells of de novo diagnosed ALL patients and chromosomal aberrations revealed by standard cytogenetic analysis, as well as to verify hidden abnormalities in the case of discrepancies between cytogenetic data and molecular analysis of the STR profile of the tumor.

Materials and methods

Analysis of STR profiles of tumor cells was performed in 88 patients with de novo diagnosed Ph-negative ALL undergoing treatment according to the RALL-2016 protocol at the National Research Center of Hematology (Moscow, Russia). The patients were 18-55 years old, 53 men and 35 women. DNA was isolated from bone marrow samples taken from patients at diagnosis. Control DNA samples were taken from the blood of patients in complete remission and/or from the buccal epithelium. STR profiles for each pair of tumor/control samples were obtained by multiplex PCR using the COrDIS Plus kit (Gordiz, Moscow), followed by fragment analysis of PCR products on an ABI 3130 genetic analyzer (Thermofisher Scientific, USA). Chromosomal microarray (CMA) of DNA with a detected loss of heterozygosity in STR loci was performed at the Genomed molecular pathology laboratory using the Genoscan 3000 system.


Normal tumor karyotype was established for 37 patients, and abnormal karyotypes were found in 51 cases. When analyzing the STR profiles of DNA from tumor and healthy cells of each patient, we found a loss of signal from one of a pair of alleles at heterozygous STR loci in twenty patients (23%). Seven of them had a normal tumor karyotype. Also, in the case of an abnormal STR karyotype, the loci with loss of heterozygosity did not always belong to aberrant chromosomes. Chromosomal microarray revealed the presence of uniparental disomy of the shoulder, or the entire chromosome, which was cytogenetically normal, but carried an STR locus with loss of heterozygosity. In one patient with a normal karyotype, a 9p21.3 (21656682_22304230) x0 microdeletion affects the region of uniparental disomy at 9p (24.3-13.3). As a result, a cluster of MTAP, CDKN2A-AS1, CDKN2A, CDKN2B-AS1, CDKN2B genes containing three oncosuppressor genes involved in the regulation of antiproliferative and proapoptotic activities of Rb1 and p53, was completely absent from the tumor cell genome. Preliminary analysis had shown, that the LOH presents a significance risk factor for dismal prognosis. [HR= 4.1 (ci95 1.1-15.6)].


Analysis of STR-profile in the tumor cells confirms and supplements the data of cytogenetic analysis, and also reveals abnormal karyotype in the absence of mitoses in the sample. Moreover, LOH detection in cases of normal tumor karyotype reveals the phenomenon of uniparental disomy, hidden chromosomal aberration, which is often the cause for transition of oncogenic mutations to homozygous form, thus aggravating prognosis of the disease.


This study was supported by a Rakfond grant 5/2019.


Loss of heterozygosity (LOH), de novo diagnosed ALL, hidden chromosomal abnormalities, uniparental disomy.

Volume 9, Number 3

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doi 10.18620/ctt-1866-8836-2020-9-3-1-152

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