Microsatellite instability assessment in prediction of drug resistance in childhood Burkitt's and large cell diffuse malignant non-Hodgkin lymphoma (MNHL)

Abstract

Background: Genomic instability may, especially with DNA directed treatment, be associated with increased therapeutic response; absence may be associated with drug resistance. In childhood MNHL, drug response is variable. At present the degree of presence of microsatellite variation, i.e., intrinsic DNA instability is not known.

Aims: To determine presence and range of microsatellite variability in common childhood MNHL.

Methods: 1.3.1. Study Populations. Consecutive, unselected (1976-96) cases of childhood Large Cell diffuse, N = 16; (9T,7B), age range 1y5m-16y8m; Burkitt's Lymphoma, n = 13, age range 4y2m-14y. Non-malignant/pre-treatment tissue of 20 cases, 13 LC, 7 Burkitt's MNHL. 1.3.2. Molecular Pathology. Routine DNA extraction, amplifications at loci D3S 1304 and D3S1537 (both closely distal to VHL, tumour suppressor gene); ELN gene D7S1870; IFNA D1S243 (1p36) which show microsatellite variation. Isotopic labelling in amplification, non-denaturing gel electrophoresis, autoradiography.

Results: Microsatellite variability was found 3/16 LC and 2/13 Burkitt's MNHL. LC MNHL, 4 abnormal areas: n = 1, 3 abnormal areas: n = 1, 2 abnormal areas n = 1; Burkitt's MNHL, 3 abnormal areas: n = 1, 1 abnormal area n = 1. No variability was found in the normal (constitutional) DNA of any of the 20 patients studied.

Conclusions: Microsatellite variability occurred in 5/29 patients with common types of childhood MNHL, indicating a limited contribution to reduced drug resistance through this mechanism.