Department of Oncology and Hematology, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy.
Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy.
Curr Oncol Rep. 2022 Jul;24(7):843-860. doi: 10.1007/s11912-022-01213-3. Epub 2022 Mar 23.
The present narrative systematic review summarizes current knowledge on germline gene mutations predisposing to solid tumors in adolescents and young adults (AYAs).
AYAs with cancer represent a particular group of patients with specific challenging characteristics and yet unmet needs. A significant percentage of AYA patients carry pathogenic or likely pathogenic variants (PV/LPVs) in cancer predisposition genes. Nevertheless, knowledge on spectrum, frequency, and clinical implications of germline variants in AYAs with solid tumors is limited. The identification of PV/LPV in AYA is especially critical given the need for appropriate communicative strategies, risk of second primary cancers, need for personalized long-term surveillance, potential reproductive implications, and cascade testing of at-risk family members. Moreover, these gene alterations may potentially provide novel biomarkers and therapeutic targets that are lacking in AYA patients. Among young adults with early-onset phenotypes of malignancies typically presenting at later ages, the increased prevalence of germline PV/LPVs supports a role for genetic counseling and testing irrespective of tumor type.
本综述性叙述总结了目前关于青少年和年轻成人（AYA）中易患实体瘤的种系基因突变的知识。
患有癌症的 AYA 代表了一组具有特定挑战性特征和未满足需求的特殊患者群体。相当一部分 AYA 患者携带有致病性或可能致病性的癌症易感性基因突变（PV/LPVs）。然而，AYA 中种系变异的谱、频率和临床意义的知识是有限的。鉴于需要适当的沟通策略、第二原发癌的风险、个性化的长期监测的需求、潜在的生殖影响以及高危家庭成员的级联检测，因此在 AYA 中识别出 PV/LPV 尤为重要。此外，这些基因突变可能为 AYA 患者提供缺乏的新型生物标志物和治疗靶点。在通常在较晚年龄出现早发恶性肿瘤表型的年轻成人中，种系 PV/LPVs 的患病率增加支持了遗传咨询和检测的作用，无论肿瘤类型如何。
