Although dic(9;20)(p13.2;q11.2) is a characteristic abnormality in childhood B-cell precursor acute lymphoblastic leukemias (BCP ALL), little is known about its clinical impact or the type and frequency of additional aberrations it may occur together with. We here review the clinical and cytogenetic features of a Nordic pediatric series of 24 patients with dic(9;20)-positive BCP ALL diagnosed 1996-2006, constituting 1.3% of the BCP ALL, as well as 47 childhood cases from the literature. Consistent immunophenotypic features of the Nordic cases included positivity for HLA-DR, CD10, CD19, CD20, and CD22 and negativity for T-cell and myeloid markers; no detailed immunophenotypes were reported for the previously published cases. In the entire cohort of 71 cases, the modal chromosome distribution was 45 (62%), 46 (21%), 47 (7%), 48 (4%), 49 (3%), 44 (1%), and 50 (1%). Additional changes were present in 63%, the most frequent of which were homozygous loss of CDKN2A (33%) and gains of chromosomes 21 (28%) and X (10%). The median patient age was 3 years, the female/male ratio was 2.0, the median white blood cell count was 24 x 10(9)/l, 11% had central nervous system involvement, and 5% had a mediastinal mass at diagnosis. Risk group stratification was nonstandard risk in 79%. The event-free survival and overall survival at 5 years for the 24 Nordic cases was 0.62 and 0.82, respectively. Thus, although relapses are quite common, postrelapse treatment of many patients is successful.

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.

Epidemiological evidence suggests that childhood acute lymphoblastic leukaemia (ALL) may be initiated by an in infection in utero. Adenovirus DNA was detected in 13 of 49 neonatal blood spots from ALL patients but only in 3 of 47 controls (P ¼ 0.012) suggesting a correlation between prenatal adenovirus infection and the development of ALL

Background: Diseases with an onset during childhood or adult life can have their origin during fetal life or at birth. Neonatal blood dried on filter paper (Guthrie cards) collected for screening purposes is routinely stored for decades. In addition to clinical use, these filters in combination with patient registers constitute an invaluable resource for epidemiological and pathophysiological research. Although RNA has been successfully recovered from such filters even after decades of storage, the potential decay of RNA over time has not previously been investigated using quantitative methods. Methods: Filter papers (ns5) with dried blood spots from the Swedish National PKU register, stored for 1, 5, 10, 15 or 20 years were randomly selected. RNA was isolated from each sample, quantitated by spectrophotometry and reverse transcribed following DNase I treatment. Amplifiable cDNA was subsequently detected by real-time PCR using primers specific for transcripts encoding b-actin. Results: Transcripts encoding b-actin were detected in all 25 samples analyzed at a mean threshold cycle (Ct) of 25 (SD 1.9). A one-way ANOVA indicated no significant effect of storage time on Ct values. Conclusions: The lack of significant decay of RNA in dried blood filters stored for up to 20 years suggests that such filters are useful for studies of RNA determinants of diseases with an onset in childhood as well as adult life.