Seipel Amanda H, Whitington Thomas, Delahunt Brett, Samaratunga Hemamali, Mayrhofer Markus, Wiklund Peter, Grönberg Henrik, Lindberg Johan, Egevad Lars
Department of Oncology-Pathology, Karolinska Institutet, 171 76 Stockholm, Sweden.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 77 Stockholm, Sweden.
Hum Pathol. 2017 Nov;69:1-7. doi: 10.1016/j.humpath.2017.04.015. Epub 2017 Apr 27.
Despite being discovered almost 50 years ago, little is known regarding the genetic profile of ductal adenocarcinoma of the prostate (DAC). In recent years, progress has been made in the understanding of the genetics of acinar adenocarcinomas, and at least 7 genetically different subtypes have been identified. DAC is known to present at an advanced stage with a high rate of extraprostatic extension and seminal vesicle invasion, and a decreased interval to biochemical recurrence and the development of metastatic disease when compared with acinar adenocarcinoma. Our aim was to investigate the genetic profile of DAC to determine whether there is a genomic rationale for the aggressive behavior associated with this tumor type. Frozen tissue from 11 cases of DAC with paired benign tissue was analyzed. After DNA extraction, copy-number alteration analysis was performed, as well as identification of mutations and indels. We compared the fraction of the DAC genome with copy-number alteration to previous results from 74 primary acinar adenocarcinomas of the prostate. The alteration rate in DAC was comparable to that of acinar adenocarcinoma of high Gleason score. DAC harbored somatic changes seen in advanced and/or metastatic castration-resistant acinar adenocarcinoma, which likely accounts for its aggressive biological behavior.
尽管前列腺导管腺癌(DAC)在近50年前就已被发现,但关于其基因特征却知之甚少。近年来,在前列腺腺泡腺癌的遗传学研究方面取得了进展,至少已鉴定出7种基因不同的亚型。已知DAC多在晚期出现,前列腺外扩展和精囊侵犯的发生率较高,与腺泡腺癌相比,其生化复发间隔时间缩短,转移疾病发生率增加。我们的目的是研究DAC的基因特征,以确定这种肿瘤类型的侵袭性行为是否存在基因组学依据。对11例DAC的冷冻组织及其配对的良性组织进行了分析。提取DNA后,进行了拷贝数改变分析以及突变和插入缺失的鉴定。我们将DAC基因组中拷贝数改变的比例与之前74例原发性前列腺腺泡腺癌的结果进行了比较。DAC的改变率与高Gleason评分的腺泡腺癌相当。DAC存在于晚期和/或转移性去势抵抗性腺泡腺癌中出现的体细胞变化,这可能解释了其侵袭性生物学行为。