Munich Leukemia Laboratory, Munich Interdisciplinary Clinic for Stem Cell Transplantation, Max-Lebsche-Platz 31, Munich, Germany.
Br J Haematol. 2010 Oct;151(1):25-36. doi: 10.1111/j.1365-2141.2010.08299.x. Epub 2010 Jul 22.
14q-deletions have been repeatedly described in mature B-cell neoplasms, but not yet characterized in a larger cohort. Based on chromosome banding analysis, the present study identified 47 del(14q) cases in 3054 mature B-cell neoplasms (1·5%) (chronic lymphocytic leukaemia [CLL]: 1·9%; CLL/prolymphocytic leukaemia [PL]: 9·0%; others: 0·2%). Interphase fluorescence in situ hybridization was performed with probes for 14q22.1, 14q24.1, 14q32.33, and IGH@ (14q32.3). The del(14q) had heterogeneous size but showed a breakpoint cluster at the centromeric site in 14q24.1 (62% of cases). At the telomeric side, the most frequent breakpoint was within the IGH@ locus (14q32.3) between IGH@ 3'-flanking and IGHV (IgVH) probes (45%). In 16 cases (34%), breakpoints occurred within 14q24.1 and 14q32.3. Eighty-one percent of del(14q) cases showed 1-3 additional cytogenetic alterations (in 45%, +12), and 56% were IGHV-unmutated. In all cases (16/16) with breakpoints in 14q24.1 and 14q32.3, a B-CLL immunophenotype was found. Clinical follow-up in 32 del(14q) patients was compared to 383 CLL and CLL/PL patients without del(14q). While 3-year-overall survival did not differ significantly, time to treatment was significantly shorter in the del(14q) cohort (21·0 months vs. 80·1 months, P = 0·015). In conclusion, the del(14q) is a rare recurrent alteration in diverse mature B-cell neoplasms, shows variable size but distinct clustering of breakpoints, and is associated with short time to treatment.
14q 缺失已在成熟 B 细胞肿瘤中反复描述，但尚未在更大的队列中进行特征描述。基于染色体带分析，本研究在 3054 例成熟 B 细胞肿瘤（1.5%）（慢性淋巴细胞白血病[CLL]：1.9%；CLL/原淋巴细胞白血病[PL]：9.0%；其他：0.2%）中鉴定了 47 例 del(14q)病例。使用针对 14q22.1、14q24.1、14q32.33 和 IGH@（14q32.3）的探针进行间期荧光原位杂交。del(14q)具有异质性大小，但在 14q24.1 处显示出着丝粒位点的断裂簇（62%的病例）。在端粒侧，最常见的断裂点位于 IGH@ 基因座（14q32.3）内，位于 IGH@3'-侧翼和 IGHV（IgVH）探针之间（45%）。在 16 例（34%）病例中，断裂点发生在 14q24.1 和 14q32.3 内。81%的 del(14q)病例显示 1-3 种额外的细胞遗传学改变（45%，+12），56%为 IGHV 未突变。在所有（16/16）发生在 14q24.1 和 14q32.3 的断裂点的病例中，均发现 B-CLL 免疫表型。对 32 例 del(14q)患者的临床随访与 383 例无 del(14q)的 CLL 和 CLL/PL 患者进行比较。虽然 3 年总生存率无显著差异，但 del(14q)组的治疗时间明显缩短（21.0 个月 vs. 80.1 个月，P = 0.015）。总之，del(14q)是一种罕见的复发性改变，在多种成熟 B 细胞肿瘤中发生，具有可变的大小，但断裂点明显聚集，并与治疗时间短有关。
