Scheurlen W G, Schwabe G C, Seranski P, Joos S, Harbott J, Metzke S, Döhner H, Poustka A, Wilgenbus K, Haas O A
Department of Pediatrics, University of Mannheim, Germany.
Genes Chromosomes Cancer. 1999 Jul;25(3):230-40. doi: 10.1002/(sici)1098-2264(199907)25:3<230::aid-gcc5>3.0.co;2-e.
Isochromosomes are monocentric or dicentric chromosomes with homologous arms that are attached in a reverse configuration as mirror images. With an incidence of 3-4%, the i(17q) represents the most frequent isochromosome in human cancer. It is found in a variety of tumors, particularly in blast crisis of chronic myeloid leukemia (CML-BC), acute myeloid leukemia (AML), non-Hodgkin's lymphoma (NHL), and medulloblastoma (MB), and indicates a poor prognosis. To determine the breakpoints on the molecular genetic level, we analyzed 18 neoplasms (six CML, four AML, one NHL, and seven MB) with an i(17q) and two MB with a pure del(17p) applying fluorescence in situ hybridization (FISH) with yeast artificial chromosome (YAC) clones, P1-artificial chromosome (PAC) clones, and cosmids from a well-characterized contig covering more than 6 Mb of genomic DNA. We identified four different breakpoint cluster regions. One is located close to or within the centromere of chromosome 17 and a second in the Charcot-Marie-Tooth (CMT1A) region at 17(p11.2). A third breakpoint was found telomeric to the CMT1A region. The fourth, most common breakpoint was detected in MB, AML, and in CML-BC specimens and was bordered by two adjacent cosmid clones (clones D14149 and M0140) within the Smith-Magenis syndrome (SMS) region. These results indicate that the low copy number repeat gene clusters which are present in the CMT and SMS regions may be one of the factors for the increased instability that may trigger the formation of an i(17q).
等臂染色体是单着丝粒或双着丝粒染色体，其同源臂以镜像的反向构型相连。i(17q)的发生率为3% - 4%，是人类癌症中最常见的等臂染色体。它存在于多种肿瘤中，尤其是慢性髓性白血病急变期（CML - BC）、急性髓性白血病（AML）、非霍奇金淋巴瘤（NHL）和髓母细胞瘤（MB），提示预后不良。为了在分子遗传学水平确定断点，我们应用荧光原位杂交（FISH）技术，使用酵母人工染色体（YAC）克隆、P1人工染色体（PAC）克隆以及来自一个特征明确的重叠群的黏粒，该重叠群覆盖超过6 Mb的基因组DNA，分析了18例带有i(17q)的肿瘤（6例CML、4例AML、1例NHL和7例MB）以及2例带有纯合17p缺失的MB。我们鉴定出四个不同的断点簇区域。一个位于17号染色体着丝粒附近或内部，另一个位于17(p11.2)的夏科 - 马里 - 图斯（CMT1A）区域。第三个断点位于CMT1A区域的端粒侧。第四个也是最常见的断点在MB、AML和CML - BC标本中检测到，位于史密斯 - 马吉尼斯综合征（SMS）区域内两个相邻的黏粒克隆（克隆D14149和M0140）之间。这些结果表明，CMT和SMS区域中存在的低拷贝数重复基因簇可能是导致不稳定性增加从而触发i(17q)形成的因素之一。
