title: Rescue of genomic information in adult acute lymphoblastic leukaemia (ALL) with normal/failed cytogenetics: a GIMEMA centralized biological study.
abstract: 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). 25/40 patients with T-ALL (62.5%) showed 77 imbalances, with at least 1 genomic imbalance and a mean of 3 aberrations/patient (range 1-12). 13/32 patients with B-ALL (40.6%) presented 34 imbalances, with a mean of 2.6 imbalances (range 1-8). A-CGH detected 4 more T-ALL cases with genomic imbalances. A-CGH identified NF1/17q11.2 deletion and interphase fluorescence in situ hybridization provided a 10.8% estimated overall incidence of NF1/17q11.2 deletion in T-ALL. In all but one case (6/7) with NF1 deletion, denaturing high-performance liquid chromatography and direct sequencing detected NOTCH1 gene mutations. Three or more imbalances in CGH-positive cases were significantly associated with resistance to treatment and death during or after induction therapy. We suggest that the work-up for ALL at diagnosis should include CGH investigations, particularly when cytogenetics is uninformative, because they may provide potentially valuable information with prognostic and therapeutic implications.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Perugia, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Matteucci
authors.forename: Gianluca
authors.initials: G
authors.lastname: Barba
authors.forename: Emanuela
authors.initials: E
authors.lastname: Varasano
authors.forename: Antonella
authors.initials: A
authors.lastname: Vitale
authors.forename: Marco
authors.initials: M
authors.lastname: Mancini
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Testoni
authors.forename: Antonio
authors.initials: A
authors.lastname: Cuneo
authors.forename: Giovanna
authors.initials: G
authors.lastname: Rege-Cambrin
authors.forename: Loredana
authors.initials: L
authors.lastname: Elia
authors.forename: Roberta
authors.initials: R
authors.lastname: La Starza
authors.forename: Valentina
authors.initials: V
authors.lastname: Pierini
authors.forename: Lucia
authors.initials: L
authors.lastname: Brandimarte
authors.forename: Marco
authors.initials: M
authors.lastname: Vignetti
authors.forename: Robin
authors.initials: R
authors.lastname: Foà
authors.forename: Cristina
authors.initials: C
authors.lastname: Mecucci
mesh_terms: D000293:Adolescent; D000328:Adult; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D005260:Female; D017353:Gene Deletion; D016514:Genes, Neurofibromatosis 1; D016678:Genome; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008297:Male; D008677:Metaphase / Q000235:genetics; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D055815:Young Adult