Lehmann Ulrich, Jung Andreas
Institut für Pathologie, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Deutschland.
Pathologisches Institut, Medizinische Fakultät, LMU München, Thalkirchner Str. 36, 80337, München, Deutschland.
Pathologe. 2021 Jul;42(4):363-368. doi: 10.1007/s00292-021-00953-6. Epub 2021 Jun 25.
The enormous increase in sequencing capacity due to the development of next generation sequencing technologies opens up new opportunities in the fields of histopathology, research, and diagnostics, but also poses huge challenges.The identification of genomic aberrations (point mutations, small insertions and deletions, fusion transcripts, and tumor mutation burden (TMB)) have already become a reliable part of routine molecular diagnostics. This will be supplemented by additional applications, namely gene amplifications, microsatellite instability, genomic signatures like homologous recombination deficiency (HRD), mRNA expression patterns, B‑ and T‑cell clonality, and DNA methylation. Challenges in preanalytics and the evaluation of assay sensitivity and specificity as well as proper curation of identified aberrations, which requires a new type of specialist, are presented and discussed.
下一代测序技术的发展使测序能力大幅提高，这在组织病理学、研究和诊断领域带来了新机遇，但也带来了巨大挑战。基因组畸变（点突变、小插入和缺失、融合转录本以及肿瘤突变负荷（TMB））的识别已成为常规分子诊断中可靠的一部分。这将通过其他应用得到补充，即基因扩增、微卫星不稳定性、诸如同源重组缺陷（HRD）等基因组特征、mRNA表达模式、B细胞和T细胞克隆性以及DNA甲基化。本文介绍并讨论了分析前阶段的挑战、检测灵敏度和特异性的评估以及对已识别畸变的正确整理，这需要新型专业人员。
