Key Points. 1. We identified a new pediatric type of PCNS-LBCL that has distinct molecular features compared to PCNS-LBCL occurring in adults.2. Pediatric PCNS-

Background: Abnormalities of chromosome 16 are found in about 5–8% of acute myeloid leukemia (AML). The AML with inv(16)(p13.1q22) or t (16;16)(p13.1;q22) is associated with a high rate of complete remission (CR) and favorable overall survival (OS) when treated with high-dose Cytarabine. At the inversion breakpoints, deletion of 3’CBFB has been reported, but most of them were studied by chromosome and fluorescence in situ hybridization (FISH) analyses. The genomic characteristics of such deletions remain largely undefined, hindering further understanding of the clinical significance of the deletions. Case presentation: We report here two AML cases with inv(16) and deletion of the 5’MYH11/3’CBFB gene fusion, which were characterized by chromosome, FISH, and single nucleotide polymorphism (SNP) microarray analyses. Both cases have achieved CR for more than three years. Conclusions: Deletion of 3’CBFB in AML with inv(16) is also accompanied with deletion of 5’MYH11 in all the cases studied by SNP microarray, suggesting that 3’CBFB and 5’MYH11 were most likely deleted together as a fusion product of inv(16) instead of occurring separately. In concert with the findings of other published studies of similar patients, our study suggests that deletion of 5’MYH11/3’CBFB in AML with inv(16) may not have negative impact on the prognosis of the disease.

Chromosome 6pter-p24 deletion syndrome (OMIM #612582) is a recognized chromosomal disorder. Most of the individuals with this syndrome carry a terminal deletion of the short arm of chromosome 6 (6p) with a breakpoint within the 6p25.3p23 region. An approximately 2.1 Mb terminal region has been reported to be responsible for some major features of the syndrome. The phenotypic contributions of other deleted regions are unknown. Interstitial deletions of the region are uncommon, and reciprocal interstitial duplication in this region is extremely rare. We present a family carrying an interstitial deletion and its reciprocal duplication within the 6p25.1p24.3 region. The deletion is 5.6 Mb in size and was detected by array comparative genomic hybridization (aCGH) in a 26-month-old female proband who presented speech delay and mild growth delay, bilateral conductive hearing loss and dysmorphic features. Array CGH studies of her family members detected an apparently mosaic deletion of the same region in the proband’s mildly affected mother, but a reciprocal interstitial duplication in her phenotypically normal brother. Further chromosomal and fluorescence in situ hybridization (FISH) analyses revealed that instead of a simple mosaic deletion of 6p25.1p24.3, the mother actually carries three cell populations in her peripheral blood, including a deletion (~70 %), a duplication (~8 %) and a normal (~22 %) populations. Therefore, both the deletion and duplication seen in the siblings were apparently inherited from the mother. Interstitial deletion within the 6p25.1p24.3 region and its reciprocal duplication may co-exist in the same individual and/or family due to mitotic unequal sister chromatid exchange. While the deletion causes phenotypes reportedly associated with the chromosome 6pter-p24 deletion syndrome, the reciprocal duplication may have no or minimal phenotypic effect, suggesting possible triploinsensitivity of the same region. In addition, the cells with the duplication may compensate the phenotypic effect of the cells with the deletion in the same individual as implied by the maternal karyotype and her mild phenotype. Chromosomal and FISH analyses are essential to verify abnormal cytogenomic array findings.

ETV6::ABL1 gene fusion is a rare recurrent genomic rearrangement associated with hematologic malignancies, and frequently occurs with additional anomalies. Due to the opposite chromosome orientations of the ETV6 and ABL1 genes, an oncogenic in-frame ETV6::ABL1 gene fusion cannot be formed by a simple translocation. The molecular mechanism of the ETV6::ABL1 fusion and the significance of co-occurring anomalies are not fully understood. We characterized genomic alterations in an individual with ETV6::ABL1 gene-fusion-positive myeloid neoplasm using various genomic technologies. Our findings uncovered a molecular mechanism of the ETV6::ABL1 fusion, in which a paracentric inversion within the short arm of chromosome 12 (12p) and a translocation between the long arm of a chromosome 9 and the 12p with the inversion were involved. In addition, we detected multiple additional anomalies in the individual, and our findings suggested that the ETV6::ABL1 fusion occurred as a secondary event in a subset of cells with the additional anomalies. We speculate that the additional anomalies may predispose to further pathogenic changes, including ETV6::ABL1 fusion, leading to neoplastic transformation.

Interstitial deletion in the long arm of chromosome 9 [del(9q)] is a fairly common cytogenetic finding associated with acute myeloid leukemia (AML), seen in approximately 2–5% of AML patients. However, the genomic features of the deletion remain largely unknown. Using chromosome analysis, single nucleotide polymorphism microarray, and next-generation sequencing, we characterized del(9q)s and other genomic alterations in 9 AML patients. We found several distinct features of the del(9q)s. The proximal breakpoints of the deletions are clustered within a 2.5-Mb region (chr9: 68,513,625–70,984,372; GRCh37) enriched with segmental duplications, which may represent a “hotspot” for genomic rearrangements. However, the distal breakpoints of the deletions vary significantly. In addition, the overall deleted region could be divided into a 14.4-Mb proximal constitutional region (chr9: 70,950,015–85,397,699; 9q21.11q21.32) and a 24.0-Mb distal oncogenic region (chr9: 85,397,700–109,427,261; 9q21.32q31.1). We further identified a 6.8-Mb common overlapped deletion region (CODR) in the distal region (chr9: 90,590,650–97,366,400). This CODR carries multiple genes that are reportedly involved in cancer pathogenesis. The prognostic value of the del(9q) in AML apparently depends on additional genomic alterations in the patients.