title: Multiple recurrent chromosomal breakpoints in mantle cell lymphoma revealed by a combination of molecular cytogenetic techniques.
abstract: Mantle cell lymphoma (MCL) is genetically characterized by 11q13 translocations leading to the overexpression of CCND1, and additional secondary genomic alterations that may be important in the progression of this disease. We have analyzed 22 MCL cases and 10 MCL cell lines using multicolor fluorescence in situ hybridization (M-FISH), FISH, and comparative genomic hybridization (CGH). The 19 cases with abnormal karyotype showed the t(11;14)(q13;q32) translocation and, additionally, 89% of cases showed both numerical (n = 58) and structural (n = 77) aberrations. All but one MCL cell line showed t(11;14) and structural and numerical alterations in highly complex karyotypes. Besides 11 and 14, the most commonly rearranged chromosomes were 1, 8, and 10 in the tumors and 1, 8, and 9 in the cell lines. No recurrent translocations other than the t(11;14) were identified. However, we identified 17 recurrent breakpoints, the most frequent being 1p22 and 8p11, each observed in four cases and two cell lines. Interestingly, five tumors and four cell lines displayed a complex t(11;14), cryptic in one case and two cell lines, preferentially involving chromosome 8. In typical MCL, ATM gene deletions were significantly associated with a high number of structural and numerical alterations. In conclusion, MCL does not have recurrent translocations other than t(11;14), but shows recurrent chromosomal breakpoints. Furthermore, most MCL harbor complex karyotypes with a high number of both structural and numerical alterations affecting several common breakpoints, leading to various balanced and unbalanced translocations.
authors: Department of Pathology, Hematopathology Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi I Sunyer, University of Barcelona, Barcelona, Spain.
authors: Itziar
authors: I
authors: Salaverria
authors: Blanca
authors: B
authors: Espinet
authors: Ana
authors: A
authors: Carrió
authors: Dolors
authors: D
authors: Costa
authors: Laura
authors: L
authors: Astier
authors: Julia
authors: J
authors: Slotta-Huspenina
authors: Leticia
authors: L
authors: Quintanilla-Martinez
authors: Falko
authors: F
authors: Fend
authors: Francesc
authors: F
authors: Solé
authors: Dolors
authors: D
authors: Colomer
authors: Sergio
authors: S
authors: Serrano
authors: Rosa
authors: R
authors: Miró
authors: Sílvia
authors: S
authors: Beà
authors: Elías
authors: E
authors: Campo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019457:Chromosome Breakage; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D020732:Cytogenetic Analysis; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D020522:Lymphoma, Mantle-Cell / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D014178:Translocation, Genetic