Yannakou Costas K, Jones Kate, Ryland Georgina L, Thompson Ella R, Reid Gareth, McBean Michelle, Trainer Alison, Westerman David, Blombery Piers
Peter MacCallum Cancer Centre, Melbourne, Australia.
University of Melbourne, Melbourne, Australia.
J Clin Pathol. 2018 Jan;71(1):84-87. doi: 10.1136/jclinpath-2017-204481. Epub 2017 Aug 11.
Massively parallel sequencing (MPS) technology has become routinely available for diagnosis, prognostication and therapeutic decision-making in haematological malignancies. However, increased throughput and wider coverage of genes can have unintended consequences. Germline variants of potential clinical significance (GVPCSs) detected during cancer testing may have implications for patients and families beyond the biological evaluation of a specific tumour. 721 reports generated from MPS panels used in the routine testing of myeloid and lymphoid malignancies were reviewed and variants within genes of potential germline relevance (, , and in all contexts and , and in the setting of juvenile myelomonocytic leukaemia) were analysed. A variant allele fraction threshold of ≥33.09% for considering germline origin of variants within cancer samples was established. The detection rate of incidental, pathogenic germline variants was 0.42%. Patient education and confirmatory germline sample testing of GVPCSs in appropriate circumstances are recommended.
大规模平行测序（MPS）技术已常规用于血液系统恶性肿瘤的诊断、预后评估和治疗决策。然而，更高的通量和更广泛的基因覆盖可能会产生意想不到的后果。癌症检测过程中检测到的具有潜在临床意义的种系变异（GVPCSs）可能对患者及其家庭产生超出特定肿瘤生物学评估的影响。对用于髓系和淋巴系恶性肿瘤常规检测的MPS检测板生成的721份报告进行了审查，并分析了具有潜在种系相关性的基因内变异（在所有情况下的 、 、 和 ，以及青少年髓单核细胞白血病情况下的 、 和 ）。确定了癌症样本中变异的种系起源的变异等位基因分数阈值≥33.09%。偶然的、致病性种系变异的检出率为0.42%。建议在适当情况下对患者进行教育，并对GVPCSs进行确证性种系样本检测。
