Fluorescence in situ hybridization analyses of hematologic malignancies reveal frequent cytogenetically unrecognized 12p rearrangements
Fluorescence in situ hybridization analyses of hematologic malignancies reveal frequent cytogenetically unrecognized 12p rearrangements
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血液系统恶性肿瘤的荧光原位杂交分析揭示了频繁的细胞遗传学无法识别的 12p 重排
作者：
P. Andreasson;Bengt Johansson;R. Billström;Stanislaw Garwicz;Felix Mitelman;Mattias Höglund
对32例恶性血液病进行了12P的荧光原位杂交(FISH)研究。这些分析揭示了20例12P的结构变化，如易位、缺失、插入、倒置和扩增。在3例急性白血病中检测到ETV6重排。1例急性未分化白血病以t(4；12)(q12；p13)为唯一异常。第二例是急性髓系白血病(AML)，表现为复杂的异常，涉及9号和12号染色体。第三例，也是AML，ETV6的远端插入到11q染色体和多环染色体中，这也是11号染色体的物质，导致了可能的融合基因的扩增。这些病例中的融合伙伴仍有待确定。可以详细描述12P上的31个额外断点。这些断裂中的大多数被证明是导致染色体间重排的，可能表明到目前为止在血液系统恶性肿瘤发病机制中尚未被识别的重要基因的位置。FISH分析发现18例存在末端或间质12P缺失。七种髓系恶性肿瘤的缺失仅限于一个区域，包括ETV6和CDKN1B，据报道，这两种基因在白血病中经常丢失。在四个病例中，缺失涉及这两个基因，而两个AML显示CDKN1B缺失，但没有ETV6，这支持了之前报道的不包括该基因的缺失区域的发现。然而，1例骨髓增生异常综合征缺少一份ETV6，而不是CDKN1B。因此，我们建议在ETV6和CDKN1B基因之间的12P上存在一个最小的缺失区。
Thirty-two hematologic malignancies – nine with cytogenetically identified 12p abnormalities and 23 with whole or partial losses of chromosome 12 – were selected for fluorescence in situ hybridization (FISH) investigations of 12p. These analyses revealed structural 12p changes, such as translocations, deletions, insertions, inversions and amplification, in 20 cases. ETV6 rearrangements were detected in three acute leukemias. One acute undifferentiated leukemia had t(4;12)(q12;p13) as the sole anomaly. The second case, an acute myeloid leukemia (AML), displayed complex abnormalities involving, among others, chromosomes 9 and 12. The third case, also an AML, had an insertion of the distal part of ETV6 into chromosome arm 11q and into multiple ring chromosomes, which also contained chromosome 11 material, resulting in an amplification of a possible fusion gene. The fusion partners in these cases remain to be identified. Thirty-one additional breakpoints on 12p could be characterized in detail. The majority of these breaks were shown to result in interchromosomal rearrangements, possibly indicating the location of hitherto unrecognized genes of importance in the pathogenesis of hematologic malignancies. The FISH analyses disclosed terminal or interstitial 12p deletions in 18 cases. Seven myeloid malignancies showed deletions restricted to a region, including ETV6 and CDKN1B, which has been reported to be frequently lost in leukemias. In four cases, the deletions involved both these genes, whereas two AML displayed loss of CDKN1B but not ETV6, supporting previously reported findings indicating a region of deletion not including this gene. However, one myelodysplastic syndrome lacked one copy of ETV6 but not CDKN1B. Hence, we suggest a minimal region of deletion on 12p located between the ETV6 and CDKN1B genes.
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DOI：
10.1073/pnas.92.11.4917
发表时间：
1995-05-23
影响因子：
11.1
作者：
GOLUB, TR;BARKER, GF;GILLILAND, DG
通讯作者：
GILLILAND, DG
影响因子：
4.4
作者：
Y. Xiong;J. Menninger;D. Beach;D. Ward
通讯作者：
Y. Xiong;J. Menninger;D. Beach;D. Ward
儿童急性淋巴细胞白血病：12 号染色体短臂上 TEL 和 KIP1 区域两个不同的缺失区域的鉴定。
影响因子：
20.3
作者：
Takeuchi,S;Bartram,CR;Miller,CW;Reiter,A;Seriu,T;Zimmerann,M;Schrappe,M;Mori,N;Slater,J;Miyoshi,I;Koeffler,HP
通讯作者：
Koeffler,HP
恶性血液病中涉及人类 12 号染色体短臂的易位和缺失的荧光原位杂交图谱。
影响因子：
20.3
作者：
Kobayashi,H;Montgomery,KT;Bohlander,SK;Adra,CN;Lim,BL;Kucherlapati,RS;Donis-Keller,H;Holt,MS;LeBeau,MM;Rowley,JD
通讯作者：
Rowley,JD
影响因子：
20.3
作者：
K. Stegmaier;Shona Pendse;G. Barker;P. Bray-Ward;David C. Ward;Kate T Montgomery;Kenneth S. Krauter;Carol Reynolds;Jeffrey Sklar;Mia Donnelly;Stefan K. Bohlander;Janet D. Rowley;Stephen E. Sallan;D. Gilliland;Todd R. Golub;Bosron Ma
通讯作者：
K. Stegmaier;Shona Pendse;G. Barker;P. Bray-Ward;David C. Ward;Kate T Montgomery;Kenneth S. Krauter;Carol Reynolds;Jeffrey Sklar;Mia Donnelly;Stefan K. Bohlander;Janet D. Rowley;Stephen E. Sallan;D. Gilliland;Todd R. Golub;Bosron Ma