Background & Aims

Colorectal cancers (CRCs) are rare in adolescents and adults ages 25 years or younger. We analyzed clinical, pathology, and molecular features of colorectal tumors from adolescents and young adults in an effort to improve genetic counseling, surveillance, and, ultimately, treatment and outcomes.

Methods

We analyzed clinical data and molecular and genetic features of colorectal tumor tissues from 139 adolescents or young adults (age, ≤25 y; median age, 23 y; 58% male), collected from 2000 through 2017; tumor tissues and clinical data were obtained from the nationwide network and registry of histopathology and cytopathology and The Netherlands Cancer Registry, respectively. DNA samples from tumors were analyzed for microsatellite instability, mutations in 56 genes, and genome-wide somatic copy number aberrations.

Results

Mucinous and/or signet ring cell components were observed in 33% of tumor samples. A genetic tumor risk syndrome was confirmed for 39% of cases. Factors associated with shorter survival time included younger age at diagnosis, signet ring cell carcinoma, the absence of a genetic tumor risk syndrome, and diagnosis at an advanced stage of disease. Compared with colorectal tumors from patients ages 60 years or older in the Cancer Genome Atlas, higher proportions of tumors from adolescents or young adults were microsatellite stable with nearly diploid genomes, or contained somatic mutations in TP53 and POLE, whereas lower proportions contained mutations in APC.

Conclusions

We found clinical, molecular, and genetic features of CRCs in adolescents or young adults to differ from those of patients older than age 60 years. In 39% of patients a genetic tumor risk syndrome was identified. These findings provide insight into the pathogenesis of CRC in young patients and suggest new strategies for clinical management. Performing genetic and molecular analyses for every individual diagnosed with CRC at age 25 years or younger would aid in this optimization.

中文翻译：

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青少年和 25 岁或更年轻成人结直肠肿瘤的临床、病理学、遗传和分子特征

背景与目标

结直肠癌 (CRC) 在 25 岁或更年轻的青少年和成年人中很少见。我们分析了青少年和年轻成人结直肠肿瘤的临床、病理学和分子特征，以改善遗传咨询、监测以及最终的治疗和结果。

方法

我们分析了 2000 年至 2017 年收集的 139 名青少年或年轻成人（年龄≤25 岁；中位年龄 23 岁；58% 男性）的结直肠肿瘤组织的临床数据和分子和遗传特征；肿瘤组织和临床数据分别来自全国组织病理学和细胞病理学网络和登记处以及荷兰癌症登记处。分析了来自肿瘤的 DNA 样本的微卫星不稳定性、56 个基因的突变和全基因组体细胞拷贝数畸变。

结果

在 33% 的肿瘤样本中观察到粘液和/或印戒细胞成分。39% 的病例被确认为遗传性肿瘤风险综合征。与较短生存时间相关的因素包括诊断时年龄较小、印戒细胞癌、没有遗传性肿瘤风险综合征以及疾病晚期诊断。与癌症基因组图谱中 60 岁或以上患者的结直肠肿瘤相比，来自青少年或年轻成人的肿瘤比例较高，具有近二倍体基因组的微卫星稳定，或包含TP53和POLE体细胞突变，而较低比例包含APC突变.

结论

我们发现青少年或年轻成人 CRC 的临床、分子和遗传特征与 60 岁以上患者不同。在 39% 的患者中确定了遗传性肿瘤风险综合征。这些发现提供了对年轻患者 CRC 发病机制的深入了解，并为临床管理提出了新的策略。对每个在 25 岁或更年轻时被诊断为 CRC 的个体进行遗传和分子分析将有助于这种优化。