Nuffield Department of Surgical Sciences, University of Oxford, Oxford OX3 9DU, UK.
Oxford Centre for Histopathology Research, University of Oxford, Oxford OX3 9DU, UK.
Int J Mol Sci. 2023 Aug 12;24(16):12722. doi: 10.3390/ijms241612722.
Prostate cancer is typically of acinar adenocarcinoma type but can occasionally present as neuroendocrine and/or ductal type carcinoma. These are associated with clinically aggressive disease, and the former often arises on a background of androgen deprivation therapy, although it can also arise de novo. Two prostate cancer cases were sequenced by exome capture from archival tissue. Case 1 was de novo small cell neuroendocrine carcinoma and ductal adenocarcinoma with three longitudinal samples over 5 years. Case 2 was a single time point after the development of treatment-related neuroendocrine prostate carcinoma. Case 1 showed whole genome doubling in all samples and focal amplification of AR in all samples except the first time point. Phylogenetic analysis revealed a common ancestry for ductal and small cell carcinoma. Case 2 showed 13q loss (involving RB1) in both adenocarcinoma and small cell carcinoma regions, and 3p gain, 4p loss, and 17p loss (involving TP53) in the latter. By using highly curated samples, we demonstrate for the first time that small-cell neuroendocrine and ductal prostatic carcinoma can have a common ancestry. We highlight whole genome doubling in a patient with prostate cancer relapse, reinforcing its poor prognostic nature.
前列腺癌通常为腺泡性腺癌类型，但偶尔也会表现为神经内分泌和/或导管型癌。这些类型与临床侵袭性疾病相关，前者通常发生在雄激素剥夺治疗的背景下，但也可以是初发。对 2 例前列腺癌存档组织进行外显子捕获测序。病例 1 为初发的小细胞神经内分泌癌和导管腺癌，5 年内有 3 个纵向样本。病例 2 是在发生治疗相关的神经内分泌前列腺癌后单一时间点的样本。病例 1 所有样本均显示全基因组倍增，除了第一个时间点，所有样本均显示 AR 局灶性扩增。系统发育分析显示导管腺癌和小细胞癌具有共同的祖系。病例 2 显示在腺癌和小细胞癌区域均存在 13q 缺失（涉及 RB1），在后一个区域存在 3p 增益、4p 缺失和 17p 缺失（涉及 TP53）。通过使用高度精心挑选的样本，我们首次证明小细胞神经内分泌和导管型前列腺癌可能具有共同的祖系。我们强调了前列腺癌复发患者的全基因组倍增，这强化了其预后不良的性质。
