title: Interstitial 13q14 deletions detected in the karyotype and translocations with concomitant deletion at 13q14 in chronic lymphocytic leukemia: different genetic mechanisms but equivalent poorer clinical outcome.
abstract: Deletion of 13q14 as the sole abnormality is a good prognostic marker in chronic lymphocytic leukemia (CLL). Nonetheless, the prognostic value of reciprocal 13q14 translocations [t(13q)] with related 13q losses has not been fully elucidated. We described clinical and biological characteristics of 25 CLL patients with t(13q), and compared with 62 patients carrying interstitial del(13q) by conventional G-banding cytogenetics (CGC) [i-del(13q)] and 295 patients with del(13q) only detected by fluorescence in situ hybridization (FISH) [F-del(13q)]. Besides from the CLL FISH panel (D13S319, CEP12, ATM, TP53), we studied RB1 deletions in all t(13q) cases and a representative group of i-del(13q) and F-del(13q). We analyzed NOTCH1, SF3B1, and MYD88 mutations in t(13q) cases by Sanger sequencing. In all, 25 distinct t(13q) were described. All these cases showed D13S319 deletion while 32% also lost RB1. The median percentage of 13q-deleted nuclei did not differ from i-del(13q) patients (73% vs. 64%), but both were significantly higher than F-del(13q) (52%, P < 0.001). Moreover, t(13q) patients showed an increased incidence of biallelic del(13q) (52% vs. 11.3% and 14.9%, P < 0.001) and higher rates of concomitant 17p deletion (37.5% vs. 8.6% and 7.2%, P < 0.001). RB1 involvement was significantly higher in the i-del(13q) group (79%, P < 0.001). Two t(13q) patients (11.8%) carried NOTCH1 mutations. Time to first treatment in t(13q) and i-del(13q) was shorter than F-del(13q) (67, 44, and 137 months, P = 0.029), and preserved significance in the multivariate analysis. In conclusion, t(13q) and del(13q) patients detected by CGC constitute a subgroup within the 13q-deleted CLL patients associated with a worse clinical outcome.
authors.affiliation: Laboratori de Citogenètica Molecular, Laboratori de Citologia Hematològica, Servei de Patologia, Hospital del Mar, Barcelona, Spain; Grup de Recerca Translacional en Neoplàsies Hematològiques, Cancer Res Program, IMIM-Hospital del Mar, Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Puiggros
authors.forename: Marta
authors.initials: M
authors.lastname: Venturas
authors.forename: Marta
authors.initials: M
authors.lastname: Salido
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Blanco
authors.forename: Concepción
authors.initials: C
authors.lastname: Fernandez-Rodriguez
authors.forename: Rosa
authors.initials: R
authors.lastname: Collado
authors.forename: Alberto
authors.initials: A
authors.lastname: Valiente
authors.forename: Neus
authors.initials: N
authors.lastname: Ruiz-Xivillé
authors.forename: Ana
authors.initials: A
authors.lastname: Carrió
authors.forename: Francisco José
authors.initials: FJ
authors.lastname: Ortuño
authors.forename: Elisa
authors.initials: E
authors.lastname: Luño
authors.forename: María José
authors.initials: MJ
authors.lastname: Calasanz
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Ardanaz
authors.forename: María Ángeles
authors.initials: MÁ
authors.lastname: Piñán
authors.forename: Elisabet
authors.initials: E
authors.lastname: Talavera
authors.forename: María Teresa
authors.initials: MT
authors.lastname: González
authors.forename: Margarita
authors.initials: M
authors.lastname: Ortega
authors.forename: Isabel
authors.initials: I
authors.lastname: Marugán
authors.forename: Ana
authors.initials: A
authors.lastname: Ferrer
authors.forename: Eva
authors.initials: E
authors.lastname: Gimeno
authors.forename: Beatriz
authors.initials: B
authors.lastname: Bellosillo
authors.forename: Julio
authors.initials: J
authors.lastname: Delgado
authors.forename: José Ángel
authors.initials: JÁ
authors.lastname: Hernández
authors.forename: Jesús María
authors.initials: JM
authors.lastname: Hernández-Rivas
authors.forename: Blanca
authors.initials: B
authors.lastname: Espinet
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D059785:Karyotype; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics; D011379:Prognosis; D000072260:RNA Splicing Factors; D051881:Receptor, Notch1 / Q000235:genetics; D016160:Retinoblastoma Protein / Q000235:genetics; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000235:genetics; D014178:Translocation, Genetic
chemical_list: C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; C497761:NOTCH1 protein, human; D010750:Phosphoproteins; D000072260:RNA Splicing Factors; D051881:Receptor, Notch1; D016160:Retinoblastoma Protein; D017413:Ribonucleoprotein, U2 Small Nuclear; C112491:SF3B1 protein, human