The GNAS1 gene in myelodysplastic syndromes (MDS).

GNAS1 gene is located at the long arm of chromosome 20 (q13.32). GNAS1 gene deletion has never been investigated in MDS.

New MLLT10 gene recombinations in pediatric T-acute lymphoblastic leukemia.

The MLLT10 gene, located at 10p13, is a known partner of MLL and PICALM in specific leukemic fusions generated from recurrent 11q23 and 11q14 chromosome translocations. Deep sequencing recently identified NAP1L1/12q21 as another MLLT10 partner in T-cell acute lymphoblastic leukemia (T-ALL). In pediatric T-ALL, we have identified 2 RNA processing genes, that is, HNRNPH1/5q35 and DDX3X/Xp11.

Inv(11)(p15q22)/NUP98-DDX10 fusion and isoforms in a new case of de novo acute myeloid leukemia.

We set up a diagnostic double-color double-fusion fluorescence in situ hybridization (DCDF-FISH) assay to investigate a case of a de novo acute myeloid leukemia (AML)-M4 bearing an inv(11)(p15q22). DCDF-FISH detected the NUP98-DDX10 rearrangement as two fusion signals, at the short and the long arms of the inv(11). Reverse transcription-polymerase chain reaction (RT-PCR) and cloning experiments confirmed the NUP98-DDX10 fusion and identified two splicing fusion isoforms: the known "type II fusion," originating from the fusion of NUP98 exon 14 to DDX10 exon 7 and a new in-frame fusion transcript between NUP98 exon 15 and DDX10 exon 7, which we termed "type III fusion.

FISH analysis reveals frequent co-occurrence of 4q24/TET2 and 5q and/or 7q deletions.

We investigated TET2 deletion in 418 patients with hematological malignancies. Overall interphase FISH detected complete or partial TET2 monoallelic deletion (TET2(del)) in 20/418 cases (4.7%).

NPM1 deletion is associated with gross chromosomal rearrangements in leukemia.

Background: NPM1 gene at chromosome 5q35 is involved in recurrent translocations in leukemia and lymphoma. It also undergoes mutations in 60% of adult acute myeloid leukemia (AML) cases with normal karyotype. The incidence and significance of NPM1 deletion in human leukemia have not been elucidated.

Rescue of genomic information in adult acute lymphoblastic leukaemia (ALL) with normal/failed cytogenetics: a GIMEMA centralized biological study.

Metaphase (M-) and array (A-) Comparative Genomic Hybridization (CGH) were used to investigate 40 cases of T- and 32 of B-cell acute lymphoblastic leukaemia (ALL) with normal/failed cytogenetics. M-CGH was performed in all cases and A-CGH in 10/12 T-ALL cases with uncertain/normal M-CGH results. M-CGH was abnormal in 38/72 cases, with a total of 110 imbalances (60 gains, 50 losses).

Combined interphase fluorescence in situ hybridization elucidates the genetic heterogeneity of T-cell acute lymphoblastic leukemia in adults.

Background: Molecular lesions in T-cell acute lymphoblastic leukemias affect regulators of cell cycle, proliferation, differentiation, survival and apoptosis in multi-step pathogenic pathways. Full genetic characterization is needed to identify events concurring in the development of these leukemias.

Design And Methods: We designed a combined interphase fluorescence in situ hybridization strategy to study 25 oncogenes/tumor suppressor genes in T-cell acute lymphoblastic leukemias and applied it in 23 adult patients for whom immunophenotyping, karyotyping, molecular studies, and gene expression profiling data were available.

A NUP98-positive acute myeloid leukemia with a t(11;12)(p15;q13) without HOXC cluster gene involvement.

We report a case of adult acute myeloid leukemia with a new t(11;12)(p15;q13) underlying a NUP98 rearrangement without HOXC cluster gene involvement. We designed a specific double-color double-fusion FISH assay to discriminate between this t(11;12)(p15;q13) and those producing NUP98-HOXC11 or NUP98-HOXC13. Our fluorescence in situ hybridization (FISH) showed that putative candidate partners mapping 600 kilobases centromeric to HOXC were RARG (retinoic acid receptor gamma), MFSD5 (major facilitator superfamily domain containing 5), and ESPL1 (extra spindle pole bodies homolog 1).

Totipotent stem cells bearing del(20q) maintain multipotential differentiation in Shwachman Diamond syndrome.

SBDS/7q11 gene mutations underlie the congenital Shwachman Diamond syndrome (SDS), characterized by bone marrow failure and high risk of haematological malignancies. In two cases of SDS with bone marrow failure and isolated del(20q) interphase fluorescence in situ hybridization (I-FISH) found no abnormalities in FHIT/3p14.2, IKZF1/7p13, D7S486/7q31, PTEN/10q23.

t(3;11)(q12;p15)/NUP98-LOC348801 fusion transcript in acute myeloid leukemia.

In a case of acute myeloid leukemia we report molecular cytogenetic findings of a t(3;11)(q12;p15), characterized as a new NUP98 translocation rearranging with LOC348801 at chromosome 3. NUP98 involvement was detected by fluorescence in situ hybridization. 3'-RACE-PCR showed nucleotide 1718 (exon 13) of NUP98 was fused in-frame with nucleotide 1248 (exon 2) of LOC348801.

Comparative genomic hybridization identifies 17q11.2 approximately q12 duplication as an early event in cutaneous T-cell lymphomas.

Mycosis fungoides (MF) and Sézary syndrome (SS) are primary cutaneous T-cell lymphomas (CTCL), a heterogeneous group of extranodal non-Hodgkin lymphomas. In the three cases of MF and four of SS studied, comparative genomic hybridization detected chromosomal imbalances in all SS cases and in one MF case. In all five abnormal cases, the long arm of chromosome 17 was completely or partially duplicated; in three of these five cases, it was the sole genomic event.

A common 93-kb duplicated DNA sequence at 1q21.2 in acute lymphoblastic leukemia and Burkitt lymphoma.

In three patients with acute lymphoblastic leukemia (ALL) and in another with Burkitt lymphoma (BL), conventional cytogenetics and fluorescence in situ hybridization (FISH), applied singly or in combination, showed 1q duplication in two cases of ALL with hyperdiploid karyotypes, 1q duplication resulting from an unbalanced translocation in a third case of ALL, and inv dup(1)(q) in a patient with BL. Centromeric or telomeric breakpoints and extension of the 1q duplicons varied in each case. FISH defined a minimal, common duplicated region of 93kb at band 1q21.