Kategorie: Maligní lymfomy a leukémie
Téma: Publication Only
Číslo abstraktu: PB1491
Autoři: Mgr. Lenka Krůzová; RNDr. Milena Holzerová, Ph.D.; Mgr. Martina Hrubá; Michaela Mikešová; MUDr. Renata Urbanová; doc. MUDr. Tomáš Papajík, CSc.; prof. MUDr. Karel Indrák, DrSc.; Prof. RNDr. Mgr. Marie Jarošová, CSc.
Background: The cytogenetic abnormality most frequently detected by fluorescence in situ hybridization (FISH) is deletion of 13q14 present in ~50% of patients with chronic lymphocytic leukemia (CLL). As a single aberration, deletion of 13q14 is associated with favorable prognosis. The prognostic value of other changes such as biallelic deletion of 13q14, monosomy 13 or translocation of chromosome 13 remains controversial. Efforts to clearly determine the extent of the deletion, significant genes located in the deleted region and clinical impact of the changes are still a matter of research.
Aims: To perform arrayCGH analysis of a group of patients with deletion of 13q14, to determine the extent of the deletion and to compare findings in patients with a single aberration, those with deletion of 13q14 and one additional change and those with complex aberrations. Furthermore, to determine the extent of the deleted region and to compare the extent of the deletions with certain clinical parameters.
Methods: A CLL FISH probe panel was used to investigate a group of 671 patients. Of those, 51 patients with detected deletion of 13q were examined with arrayCGH (peripheral blood in 46 pts, bone marrow in 4 pts and a lymph node in 1 pt).
Results: In the group of 671 patients, deletion of 13q14 was determined in 301 (45%) patients. Among those, arrayCGH was used to examine 14 patients with a single aberration of 13q14, 11 patients with two aberrations and 26 patients with complex changes. The subgroup comprised 38 males and 13 females with a median age of 62 years (range, 27–86 years). Seventeen patients had Binet’s stage A, 10 patients had stage B and 17 patients had stage C; in 7 patients, the stage was not specified. Unmutated and mutated IgVH genes were found in 31 and 11 patients, respectively; in 9 patients, the mutational status was not studied. A total of nine patients died. Ten patients had biallelic deletion of 13q14; this was associated with monoallelic deletion of 13q14 in 8 cases. ArrayCGH determined the smallest deleted region of 850 kb at 13q14.2-13q14.3, containing the MIR15a, MIR16-1, DLEU1, DLEU2 and DLEU7 genes. In one patient, deletion of 13q was only determined by arrayCGH at 13q21.1-q21.2 sized 1.1 Mb. Two patients had monosomy 13. Comparison of the detected deletion with certain studied parameters such as IgVH mutational status, Binet’s stage, type of deletion of 13q and additional chromosomal changes has not confirmed a direct association with the extent of the deletion as yet. Only patients with complex changes tended to have more extensive deletions.
Summary/Conclusion: The arrayCGH analysis of a group of 51 CLL patients with deletion of 13q determined by FISH confirmed a large heterogeneity of the extent of the deletion and tendency of association of large deletion with complex changes. Given the small number of patients in the study, the clinical significance of the investigated deletions of 13q cannot be clearly determined.
This work was supported by grants: IGA MZ ČR NT 13576 and IGA-LF-2014-001.
Keywords: Array based comparative genomic hybridization, Chronic lymphocytic leukemia
Datum přednesení příspěvku: 17. 6. 2014