Forestier Erik, Andersen Mette K, Autio Kirsi, Blennow Elisabeth, Borgström Georg, Golovleva Irina, Heim Sverre, Heinonen Kristina, Hovland Randi, Johannsson Johann H, Kerndrup Gitte, Nordgren Ann, Rosenquist Richard, Swolin Birgitta, Johansson Bertil
Pediatrics Unit, Department of Clinical Sciences, University of Umeå, Umeå, Sweden.
Genes Chromosomes Cancer. 2007 May;46(5):440-50. doi: 10.1002/gcc.20423.
Between 1992 and 2004, 1,140 children (1 to<15 years) were diagnosed with B-cell precursor acute lymphoblastic leukemia (ALL) in the Nordic countries. Of these, 288 (25%) were positive for t(12;21)(p13;q22) [ETV6/RUNX1]. G-banding analyses were successful in 245 (85%); 43 (15%) were karyotypic failures. The modal chromosome numbers, incidence, types, and numbers of additional abnormalities, genomic imbalances, and chromosomal breakpoints in the 245 karyotypically informative cases, as well as in 152 previously reported cytogenetically characterized t(12;21)-positive ALLs in the same age group, were ascertained. The most common modal numbers among the 397 cases were 46 (67%), 47 (16%), 48 (6%), and 45 (5%). High-hyperdiploidy, triploidy, and tetraploidy were each found in approximately 1%; none had less than 40 chromosomes. Secondary chromosomal abnormalities were identified by chromosome banding in 248 (62%) of the 397 ALLs. Of these, 172 (69%) displayed only unbalanced changes, 14 (6%) only balanced aberrations, and 26 (10%) harbored both unbalanced and balanced abnormalities; 36 (15%) were uninformative because of incomplete karyotypes. The numbers of secondary changes varied between 1 and 19, with a median of 2 additional aberrations per cytogenetically abnormal case. The most frequent genomic imbalances were deletions of 6q21-27 (18%), 8p11-23 (6%), 9p13-24 (7%), 11q23-25 (6%), 12p11-13 (27%), 13q14-34 (7%), loss of the X chromosome (8%), and gains of 10 (9%), 16 (6%), and 21 (29%); no frequent partial gains were noted. The chromosome bands most often involved in structural rearrangements were 3p21 (2%), 5q13 (2%), 6q12 (2%), 6q14 (2%), 6q16 (2%), 6q21 (10%), 6q23 (6%), 6q25 (3%), 9p13 (2%), 11q13 (2%), 11q23 (2%), 12p11 (6%), 12p12 (7%), 12p13 (25%), 21q10 (6%), and 21q22 (6%). Considering that the t(12;21) is known to arise in utero and that the postnatal latency period is protracted, additional mutations are most likely necessary for overt ALL. The frequently rearranged chromosome regions may harbor genes of importance for the transformation and/or progression of an initial preleukemic t(12;21)-positive clone.
1992年至2004年间，北欧国家有1140名儿童（1至<15岁）被诊断为B细胞前体急性淋巴细胞白血病（ALL）。其中，288名（25%）t(12;21)(p13;q22) [ETV6/RUNX1]呈阳性。245名（85%）成功进行了G显带分析；43名（15%）核型分析失败。确定了245例核型信息明确的病例以及同一年龄组中先前报道的152例经细胞遗传学特征分析的t(12;21)阳性ALL病例的众数染色体数目、发生率、额外异常的类型和数量、基因组失衡情况以及染色体断点。397例病例中最常见的众数染色体数目为46（67%）、47（16%）、48（6%）和45（5%）。高超二倍体、三倍体和四倍体各约占1%；染色体数目均不少于40条。397例ALL病例中有248例（62%）通过染色体显带鉴定出继发性染色体异常。其中，172例（69%）仅表现为不平衡改变，14例（6%）仅为平衡畸变，26例（10%）既有不平衡异常又有平衡异常；36例（15%）因核型不完整而未提供有效信息。继发性改变的数量在1至19之间，每个细胞遗传学异常病例额外畸变的中位数为2个。最常见的基因组失衡包括6q21 - 27缺失（18%）、8p11 - 23缺失（6%）、9p13 - 24缺失（7%）、11q23 - 25缺失（6%）、12p11 - 13缺失（27%）、13q14 - 34缺失（7%）、X染色体缺失（8%）以及10号染色体增加（9%）、16号染色体增加（6%）和21号染色体增加（29%）；未发现常见的部分增加情况。结构重排中最常涉及的染色体带为3p21（2%）、5q13（2%）、6q12（2%）、6q14（2%）、6q16（2%）、6q21（10%）、6q23（6%）、6q25（3%）、9p13（2%）、11q13（2%）、11q23（2%）、12p11（6%）、12p12（7%）、12p13（25%）、21q10（6%）和21q22（6%）。鉴于已知t(12;21)在子宫内发生且出生后的潜伏期较长，明显的ALL很可能还需要其他突变。频繁重排的染色体区域可能含有对初始白血病前期t(12;21)阳性克隆的转化和/或进展至关重要的基因。
