Puiggros Anna, Venturas Marta, Salido Marta, Blanco Gonzalo, Fernandez-Rodriguez Concepción, Collado Rosa, Valiente Alberto, Ruiz-Xivillé Neus, Carrió Ana, Ortuño Francisco José, Luño Elisa, Calasanz María José, Ardanaz María Teresa, Piñán María Ángeles, Talavera Elisabet, González María Teresa, Ortega Margarita, Marugán Isabel, Ferrer Ana, Gimeno Eva, Bellosillo Beatriz, Delgado Julio, Hernández José Ángel, Hernández-Rivas Jesús María, Espinet Blanca
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.
Genes Chromosomes Cancer. 2014 Sep;53(9):788-97. doi: 10.1002/gcc.22188. Epub 2014 Jun 10.
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.
13q14缺失作为唯一异常是慢性淋巴细胞白血病（CLL）的一个良好预后标志物。尽管如此，相互性13q14易位[t(13q)]及其相关的13q缺失的预后价值尚未完全阐明。我们描述了25例t(13q)的CLL患者的临床和生物学特征，并与62例通过传统G显带细胞遗传学（CGC）检测到间质13q缺失[i-del(13q)]的患者以及295例仅通过荧光原位杂交（FISH）检测到13q缺失[F-del(13q)]的患者进行了比较。除了CLL FISH检测板（D13S319、CEP12、ATM、TP53）外，我们还研究了所有t(13q)病例以及一组具有代表性的i-del(13q)和F-del(13q)病例中的RB1缺失情况。我们通过Sanger测序分析了t(13q)病例中的NOTCH1、SF3B1和MYD88突变。总共描述了25种不同的t(13q)。所有这些病例均显示D13S319缺失，而32%的病例也丢失了RB1。13q缺失核的中位百分比与i-del(13q)患者无差异（73%对64%），但两者均显著高于F-del(13q)（52%，P<0.001）。此外，t(13q)患者双等位基因13q缺失的发生率增加（52%对11.3%和14.9%，P<0.001），同时17p缺失的发生率更高（37.5%对8.6%和7.2%，P<0.001）。RB1受累在i-del(13q)组中显著更高（79%，P<0.001）。2例t(13q)患者（11.8%）携带NOTCH1突变。t(13q)和i-del(13q)患者的首次治疗时间短于F-del(13q)（67、44和137个月，P=0.029），在多变量分析中仍具有显著性。总之，通过CGC检测到的t(13q)和del(13q)患者构成了13q缺失的CLL患者中的一个亚组，其临床结局较差。
