ASSOCIATION OF MYCN GENE AMPLIFICATION AND REARRANGEMENTS OF CHROMOSOMAL REGION 1p36 AND 11q WITH EFFICACY OF NEUROBLASTOMA TREATMENT

Shymon D., Inomistova M., Skachkova O., Gorbach O., Klymnyuk G., Khranovska N.

MEDICAL GENETICS

Scentific article

Neuroblastoma (NB) is an embryonal tumor of the sympathetic nervous system, which causes 15% of pediatric cancer deaths. NB cells with MYCN amplification is one of the most aggressive NB subgroups that comprises 20-25% of all primary tumors and is associated with tumor progression with poor prognosis. 1p36 deletion is a frequent chromosomal abnormality observed in NB cell lines and primary tumors; 11q deletion is one of the most frequent events that occurs during NB aggressive development. The aim is to determine the frequency of MYCN gene amplification occurrence; also to describe the rearrangement of chromosomal region 1p36 and 11q in pediatric patients with NB; and then to investigate its association with the effectiveness of treatment. Paraffin-embedded tumor tissues of 103 patients, from 2 months old to 16 years old (54.5 ± 4,2 months), with verified NB were used in the study. All samples were analyzed on MYCN amplification and rearrangements of chromosomal regions 1p36 and 11q. Tumor samples were obtained prior to chemotherapy treatment. MYCN amplification was analyzed by FISH microscopy and real-time PCR, and deletions of 1p36 and 11q chromosomal regions were determined by FISH microscopy. In tumor tissues, 11q deletion was determined in 3.9% (4/103) of patients with NB. Deletion of the chromosomal region 1p36 was detected in 4.9% (5/103) of NB patient tumor tissues. MYCN gene amplification was detected in 35% (36/103) out of patients with NB. Amplification of the MYCN gene was detected in 2 patients (1.9%) out of 4 with detected 11q deletion, which is the most commonly observed in female (3/4) patients, older than 2 years (2/4). A statistically significant difference between groups of patients with and without deletion of the 11q chromosome, such as sex (χ2 = 0.714, p = 0.399), age (χ2 = 0.121, p = 0.94), and MYCN gene status (χ2 = 0.42, g = 0.52), was not observed. Amplification of the MYCN gene was detected in all patients with 1p36 deletion. The 1p36 deletion was detected most commonly in female (3/5) patients older than 2 years (3/5). The difference between the presence/ absence of 1p36 deletion and MYCN gene status was statistically significant (χ2 = 9.8, p = 0.002). According to the Kaplan-Meier method, the deletion of 11 chromosome’s long arm didn’t affect the duration of recurrent period, p = 0.07. Similarly, the MYCN gene amplification didn’t affect the duration of progression free period, p = 0.6. However, the deletion of the 1p36 chromosome significantly reduced the duration of relapse-free period in children with NB (p = 0.002). NB patient’s with 1p36 deletion 6-month disease-free survival was 60 ± 2%, but throughout the one year all patients with 1p36 deletion had local recurrences and/or distant metastases. Among the patients without 1p36 deletion the 6-month progression free survival rate was 90.6 ± 4% and the one-year progression free survival was 87 ± 5%. We established that only 1p36 deletion was decreased significantly progression free survival rate in patients with NB and all patients with 1p36 deletion had local recurrences and/or distant metastases in one year period.

neuroblastoma, MYCN, 11q, 1p36.

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«Bulletin of problems biology and medicine» Issue 1 (155), 2020 year, 219-223 pages, index UDK 575.224:577.29:616-006.48-092.6

10.29254/2077-4214-2020-1-155-219-223