Kowalski Jeanne, Morsberger Laura A, Blackford Amanda, Hawkins Anita, Yeo Charles J, Hruban Ralph H, Griffin Constance A
Department of Oncology, The Johns Hopkins University, Baltimore, MD, USA.
Cancer Genet Cytogenet. 2007 Oct 1;178(1):26-35. doi: 10.1016/j.cancergencyto.2007.06.004.
The high level of karyotypic complexity found in epithelial neoplasms hinders the characterization of their cytogenetic evolution. Derivation of such pathways in adenocarcinoma of the pancreas has been particularly limited, because only a few pancreatic carcinomas are resected at an early stage of disease and so the number of primary carcinomas for which analysis of abnormal karyotypes has been reported is small. Here we report the clonal karyotypic abnormalities identified by G-banding analysis of 36 primary pancreatic carcinomas obtained from patients undergoing a Whipple resection with curative intent. The majority of the 36 carcinomas were diploid or triploid (33 of 36; 91%). Numerical alterations were found in all carcinomas for which a complete karyotype was determined. All the chromosomes were involved in gain, loss, or both gain and loss of the entire chromosome, in at least 8 and up to 28 of the carcinomas. Most commonly lost were chromosomes 18 (in 78% of the 36 carcinomas), 17 (56%), 6 (44%), 21 (42%), 22 (42%), Y (36%), and 4 (33%). Gain of chromosome 20 was observed in 10 of the 36 carcinomas. Structural abnormalities were common, resulting in partial chromosomal gains and losses, with a median number of 7 partial imbalances per carcinoma (range, 1-15). Sixteen carcinomas contained double-minute chromosomes, homogeneously staining regions, or both, indicating gene amplification. Pooling data for these 36 carcinomas with the primary carcinomas with karyotypes published in the Mitelman database (http://cgap.nci.nih.gov/Chromosomes/Mitelman), we defined pathways of karyotypic evolution. The most frequent chromosomal imbalances were -18 (67.6%), -10 (34.3%), -4 (31.4%), +20 (31.4%), -15p (23.8%), -14p (22.9%), +2 (21.9%), -5 (21.9%), -13p (20%), +16 (20%), -21p (19%), -17p (19%), +1q (19.0%). Recurrent imbalances identified as occurring early were -1p, -15p, -18, -7q, -8p, -17p, and -5; late recurrent imbalances were +11q, +7q, +6p, -19p, and +2. In contrast to reports from similar analyses in other epithelial carcinomas, we did not find evidence for multiple karyotypic evolutionary pathways.
上皮性肿瘤中发现的高水平核型复杂性阻碍了对其细胞遗传学进化的特征描述。胰腺腺癌中此类途径的推导尤其有限，因为只有少数胰腺癌在疾病早期被切除，因此已报道异常核型分析的原发性癌数量很少。在此，我们报告了通过G显带分析对36例接受根治性胰十二指肠切除术患者的原发性胰腺癌所鉴定出的克隆性核型异常。36例癌中的大多数为二倍体或三倍体（36例中的33例；91%）。在所有确定了完整核型的癌中均发现了数目改变。所有染色体均参与了整条染色体的增加、缺失或既有增加又有缺失，在至少8例至多达28例癌中出现这种情况。最常缺失的染色体是18号染色体（36例癌中的78%）、17号染色体（56%）、6号染色体（44%）、21号染色体（42%）、22号染色体（42%）、Y染色体（36%）和4号染色体（33%）。在36例癌中的10例中观察到20号染色体增加。结构异常很常见，导致部分染色体的增加和缺失，每例癌中部分失衡的中位数为7个（范围为1 - 15个）。16例癌含有双微体染色体、均匀染色区或两者都有，表明存在基因扩增。将这36例癌的数据与Mitelman数据库（http://cgap.nci.nih.gov/Chromosomes/Mitelman）中已发表核型的原发性癌的数据汇总，我们定义了核型进化途径。最常见的染色体失衡为 - 18（67.6%）、 - 10（34.3%）、 - 4（31.4%）、 + 20（31.4%）、 - 15p（23.8%）、 - 14p（22.9%）、 + 2（21.9%）、 - 5（21.9%）、 - 13p（20%）、 + 16（20%）、 - 21p（19%）、 - 17p（19%）、 + 1q（19.0%）。被确定为早期出现的复发性失衡为 - 1p、 - 15p、 - 18、 - 7q、 - 8p、 - 17p和 - 5；晚期复发性失衡为 + 11q、 + 7q、 + 6p、 - 19p和 + 2。与其他上皮性癌类似分析的报告不同，我们没有发现多条核型进化途径的证据。
