Supplementary Material for: Supernumerary Isochromosome 1, idic(1)(p12), Leading to Tetrasomy 1q in Burkitt Lymphoma

Burkitt lymphoma (BL) is an aggressive mature B-cell neoplasm. The cytogenetic hallmark are <i>MYC</i>-involving translocations, most frequently as t(8;14)(q24;q32). Additional cytogenetic abnormalities are seen in the majority of cases. The most frequent additional aberration involves the long arm of chromosome 1, either as partial or complete trisomy 1q. A very rare additional aberration is a supernumerary isochromosome 1q, i(1)(q10), resulting in tetrasomy 1q. The biological significance of this aberration is unclear. We present a highly aggressive case of BL in a child with immature B-cell immunophenotype (IP) and supernumerary i(1)(q10). Diagnostic karyotyping showed 47,XY,+i(1)(q10),t(8;14)(q24;q32)[2]/47,idem,del(15)(q24)[21]/46,XY[2]. aCGH analysis detected a gain of 1p12qter and a loss of 15q22q25. FISH analysis confirmed the isodicentric chromosome 1, which has not previously been reported in BL. In the literature, supernumerary i(1)(q10) was found in 11 cases of which &gt;80% presented with immature B-cell IP and &gt;60% relapsed or died. Tetrasomy 1q resulting from supernumerary idic(1)(p12) or i(1)(q10) is a rare genetic event in BL and probably associated with immature B-cell IP. We propose that high amplification of genes on chromosome 1p12qter may contribute to the BL IP and disease progression.

伯基特淋巴瘤（Burkitt lymphoma, BL）是一种侵袭性成熟B细胞肿瘤。其细胞遗传学标志性特征为累及MYC基因的染色体易位，最常见的易位类型为t(8;14)(q24;q32)。多数病例可观察到额外的细胞遗传学异常，其中最常见的额外畸变累及1号染色体长臂，可为部分或完全性1号染色体长臂三体（trisomy 1q）。一种极为罕见的额外畸变为额外等臂染色体1q，即i(1)(q10)，可导致1号染色体长臂四体（tetrasomy 1q），该畸变的生物学意义目前尚不明确。本文报告1例儿童伯基特淋巴瘤病例，该患者表现为不成熟B细胞免疫表型（immunophenotype, IP）并携带额外i(1)(q10)。诊断性核型分析结果为：47,XY,+i(1)(q10),t(8;14)(q24;q32)[2]/47,idem,del(15)(q24)[21]/46,XY[2]。阵列比较基因组杂交（array comparative genomic hybridization, aCGH）分析检测到1p12qter区域拷贝数增加，以及15q22q25区域拷贝数丢失。荧光原位杂交（fluorescence in situ hybridization, FISH）分析确认了等双着丝粒1号染色体，该异常此前尚未在伯基特淋巴瘤中被报道。现有文献报道显示，携带额外i(1)(q10)的病例共11例，其中＞80%表现为不成熟B细胞免疫表型，＞60%出现疾病复发或死亡。由额外等双着丝粒1号染色体idic(1)(p12)或i(1)(q10)所导致的1号染色体长臂四体，在伯基特淋巴瘤中属于罕见遗传学事件，且可能与不成熟B细胞免疫表型相关。我们推测，1号染色体1p12qter区域基因的高扩增可能参与伯基特淋巴瘤的免疫表型形成及疾病进展过程。