The frequency and prognostic impact of dic(9;20)(p13.2;q11.2) in childhood B-cell precursor acute lymphoblastic leukemia: results from the NOPHO ALL-2000 trial

Abstract

The dic(9;20)(p13.2;q11.2) is reported to be present in B2% of childhood B-cell precursor acute lymphoblastic leukemia (BCP ALL). However, it easily escapes detection by G-banding analysis and its true prevalence is hence unknown. We performed interphase fluorescence in situ hybridization analysesFin a three-step mannerFusing probes for: (i) CDKN2A at 9p21, (ii) 20p and 20q subtelomeres and (iii) cen9 and cen20. Out of 1033 BCP ALLs diagnosed from 2001 to 2006, 533 were analyzed; 16% (84/533) displayed 9p21 deletions, of which 30% (25/84) had dic(9;20). Thus, dic(9;20)-positivity was found in 4.7% (25/533), making it the third most common genetic subgroup after high hyperdiploidy and t(12;21)(p13;q22). The dic(9;20) was associated with a female predominance and an age peak at 3 years; 18/25 (72%) were allocated to non-standard risk treatment at diagnosis. Including cases detected by G-banding alone, 29 dic(9;20)-positive cases were treated according to the NOPHO ALL 2000 protocol. Relapses occurred in 24% (7/29) resulting in a 5-year event-free survival of 0.69, which was significantly worse than for t(12;21) (0.87; P ¼ 0.002) and high hyperdiploidy (0.82; P ¼ 0.04). We conclude that dic(9;20) is twice as common as previously surmised, with many cases going undetected by G-banding analysis, and that dic(9;20) should be considered a non-standard risk abnormality.

Chromosomal aberrations in childhood acute lymphoblastic leukemia: 15-year single center experience

“…It is unclear whether dic(9;20) should be considered a primary aberration or not [32]. We know that this aberration, however, could easily escape detection by traditional cytogenetic approaches because of its subtle nature [32,33]. FISH with specific probes is considered to be the method of choice for reliable detection of dic (9;20) in routine clinical setting [33].…”

Disease‐associated patterns of disomic chromosomes in hyperhaploid neoplasms

“…In general, different chromosome aberrations occur at similar frequencies in men and women in most tumor entities, but some exceptions have been reported, such as del(5q) in myelodysplastic syndrome and dic(9;20)(p13;q11) in ALL being more common in females and der(1;7)(q10;p10) and t(11;17)(q23;q21) in ML being more common in men ( Van den Berghe et al, 1985;Sanada et al, 2007;Johansson and Harrison, 2009;Zachariadis et al, 2011). Whether such differences are merely due to chance or if they reflect significant biological, gender-related processes remains to be investigated.…”

High modal number and triple trisomies are highly correlated favorable factors in childhood B-cell precursor high hyperdiploid acute lymphoblastic leukemia treated according to the NOPHO ALL 1992/2000 protocols

“…1 HeH cases are generally associated with favorable clinical features, such as a low white blood cell (WBC) count, lack of extramedullary manifestations, and age between 2-5 years, and have a superior outcome, with overall survival (OS) rates exceeding 90% in most contemporary treatment protocols. [1][2][3][4][5][6][7] This notwithstanding, a substantial proportion of patients relapses, so event-free survival (EFS) rates are only 70-80%. [4][5][6][7] Several attempts have been made to define the clinical and genetic characteristics present at the time of diagnosis that would enable identification of patients who will respond poorly to standard-risk treatment and who could, therefore, benefit from more intensive therapy.…”

“…[1][2][3][4][5][6][7] This notwithstanding, a substantial proportion of patients relapses, so event-free survival (EFS) rates are only 70-80%. [4][5][6][7] Several attempts have been made to define the clinical and genetic characteristics present at the time of diagnosis that would enable identification of patients who will respond poorly to standard-risk treatment and who could, therefore, benefit from more intensive therapy. However, only a few clinical features have been shown to be associated with decreased EFS within the HeH group, namely age >10 years, male gender, and bone marrow fibrosis.…”