Trisomy 17 in congenital plexiform (multinodular) cellular schwannoma.

Plexiform (multinodular) cellular schwannomas are rare tumors, not associated with neurofibromatosis type 1, that occur more often in children and can be congenital. Their biology is benign and is characterized by the tendency to recur locally without being metastatic. Cytogenetic studies in adult cases of schwannoma indicate a complete or partial loss of chromosome 22 as the most common abnormality.

Cytogenetic characterization of a fibrous hamartoma of infancy with complex translocations.

Fibrous hamartoma of infancy is a rare pediatric superficial soft tissue lesion. The diagnosis depends on microscopic examination. Conventional cytogenetic analysis has been reported in only two previous cases, which showed apparently balanced translocations with involvement of different chromosomes.

MicroRNA-125b-1 and BLID upregulation resulting from a novel IGH translocation in childhood B-Cell precursor acute lymphoblastic leukemia.

Chromosomal translocations involving the immunoglobulin heavy chain (IGH) locus are common abnormalities in mature B-cell neoplasms. Recent findings have also revealed their significant role in B-cell precursor acute lymphoblastic leukemia. As a rule, IGH translocations generate transcriptional activation of the oncogene localized in the proximity of the breakpoint.

Differential diagnosis of lipoma-like lipoblastoma.

Lipoblastomas are rare benign tumors of white fatty tissue that occur primarily in young children. Occasionally, heterogeneity of morphological appearance and histological overlap with other lipogenic tumors are described. In such cases fluorescence in situ hybridization (FISH) analysis of PLAG1, a gene specifically rearranged in lipoblastoma, is necessary to prevent misdiagnosis.

Monitoring the isochromosome i(7)(q10) in the bone marrow of patients with Shwachman syndrome by real-time quantitative PCR.

Clonal chromosome anomalies may be found in the bone marrow (BM) of patients with Shwachman syndrome, who are at risk to develop myelodysplastic syndromes and/or acute myeloid leukemias. In particular, an isochromosome i(7)(q10) is frequent, and is usually monitored by chromosome analyses. We tested an approach by real-time quantitative polymerase chain reaction (RQ-PCR) on a chromosome 7 polymorphism.

Inversion (11)(p15q22) with NUP98-DDX10 fusion gene in pediatric acute myeloid leukemia.

The inv(11)(p15q22), a rare but recurrent chromosome abnormality that creates a NUP98-DDX10 fusion gene, is associated with de novo or secondary myeloid malignancies. We report a case of acute monocytic leukemia presenting this rearrangement, studied using fluorescence in situ hybridization (FISH) and reverse transcriptase-PCR (RT-PCR). We also review the cases of inv(11) associated with NUP98-DDX10 reported in the literature.

Gain of 1q in pediatric myelodysplastic syndromes.

The presence of acquired clonal cytogenetic abnormalities in hematopoietic cells is one of the diagnostic hallmarks of myelodysplastic syndromes (MDS). Such anomalies may help in defining prognostic groups. We analyzed eight pediatric MDS, and herein describe three new cases, one de novo and two therapy-related, presenting an unbalanced rearrangement of 1q: one of them resulted in a derivative chromosome 6 apparently identical to a previously described one.

Shwachman syndrome as mutator phenotype responsible for myeloid dysplasia/neoplasia through karyotype instability and chromosomes 7 and 20 anomalies.

An investigation of 14 patients with Shwachman syndrome (SS), using standard and molecular cytogenetic methods and molecular genetic techniques, showed that (1) the i(7)(q10) is not, or not always, an isochromosome but may arise from a more complex mechanism, retaining part of the short arm; (2) the i(7)(q10) has no preferential parental origin; (3) clonal chromosome changes, such as chromosome 7 anomalies and del(20)(q11), may be present in the bone marrow (BM) for a long time without progressing to myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML); (4) the del(20)(q11) involves the minimal region of deletion typical of MDS/AML; (5) the rate of chromosome breaks is not significantly higher than in controls, from which it is concluded that SS should not be considered a breakage syndrome; (6) a specific kind of karyotype instability is present in SS, with chromosome changes possibly found in single cells or small clones, often affecting chromosomes 7 and 20, in the BM. Hence, we have confirmed our previous hypothesis that the SS mutation itself implies a mutator effect that is responsible for MDS/AML through these specific chromosome anomalies. This conclusion supports the practice of including cytogenetic monitoring in the follow-up of SS patients.

MLL-MLLT10 fusion gene in pediatric acute megakaryoblastic leukemia.

The occurrence of MLL gene rearrangement in acute megakaryoblastic leukemia (AML-M7, acute myeloid leukemia, French-American-British type M7) is very rare and limited to pediatric age: in particular, MLL-MLLT10 fusion, previously reported as characteristic of monocytic leukemia, has been reported in only one case of pediatric megakaryoblastic leukemia. We describe the second case with this association in light of the few reported cases of AML-M7 with MLL and/or 11q23 involvement.

t(9;11)(p22;p15) with NUP98-LEDGF fusion gene in pediatric acute myeloid leukemia.

The rare t(9;11)(p22;p15) translocation is associated with adult acute myeloid leukemia (AML) with immature forms. We report a novel fusion of the NUP98 and LEDGF genes in a pediatric AML with intermediate characteristics between M2-M3 French-American-British (FAB) subtypes exhibiting the same chromosomal rearrangement. Fluorescence in situ hybridization (FISH) and reverse transcriptase-PCR (RT-PCR) studies identified the chimeric transcript product of in-frame fusion of NUP98 exon 8 to LEDGF exon 4.

MLL-MLLT10 fusion in acute monoblastic leukemia: variant complex rearrangements and 11q proximal breakpoint heterogeneity.

Cytogenetic studies of acute monoblastic leukemia cases presenting MLL-MLLT10 (alias MLL-AF10) fusion show a broad heterogeneity of chromosomal breakpoints. We present two new pediatric cases (French-American-British type M5) with MLL-MLLT10 fusion, which we studied with fluorescence in situ hybridization. In both we detected a paracentric inversion of the 11q region that translocated onto chromosome 10p12; one case displayed a variant complex pattern.

HCMOGT-1 is a novel fusion partner to PDGFRB in juvenile myelomonocytic leukemia with t(5;17)(q33;p11.2).

PDGFRB, a transmembrane tyrosine kinase receptor for platelet-derived growth factor, is constitutively activated by gene fusion with different partners in myeloproliferative/myelodysplastic disorders with peculiar clinical characteristics. Six alternative partner genes have been described thus far. In this study, we report the molecular cloning of a novel translocation t(5;17)(q33;p11.

Is t(10;11)(p11.2;q23) involving MLL and ABI-1 genes associated with congenital acute monocytic leukemia?

Congenital, or perinatal, leukemias are rarely observed, but retrospective molecular studies seem to suggest a more frequent onset in prenatal life. Myelocytic types are common, and chromosome band 11q23 rearrangements at the MLL locus are characteristic genetic markers. The fusion of the MLL gene with one of its partners, ABI-1, has recently been described in two infant leukemia patients with monocytic involvement and good clinical outcome.

Cryptic translocation t(5;11)(q35;p15.5) with involvement of the NSD1 and NUP98 genes without 5q deletion in childhood acute myeloid leukemia.

The cryptic translocation t(5;11)(q35;p15.5), which creates a NSD1-NUP98 fusion gene, has been associated with a deletion of the long arm of chromosome 5, del(5q), in pediatric acute myeloid leukemia (AML) patients with differentiated phenotype. We screened five pediatric cases of AML with apparently normal karyotype by use of fluorescence in situ hybridization analysis and detected one case with early myeloid phenotype and poor clinical outcome, but with the same breakpoints and no del(5q).

XY female with a dysgerminoma and no mutation in the coding sequence of the SRY gene.

We report a 46,XY 11-year-old girl with pure gonadal dysgenesis who developed a dysgerminoma. The testis-determining gene SRY, a candidate for sex reversal, whose alterations seem to correlate with dysgerminoma, was analyzed and found to be normal; its coding sequence was negative for deletions and mutations. DMRT-1 gene mapping on 9p and DAX-1 on Xp21 were also normal.