The role of molecular profiling in the diagnosis and management of metastatic undifferentiated cancer of unknown primary✰

基因表达谱 医学 计算生物学 临床试验 病理 分子诊断学 仿形(计算机编程) DNA甲基化 生物信息学 肿瘤科 生物 基因 基因表达 遗传学 计算机科学 操作系统
作者
Josephine K. Dermawan,Brian P. Rubin
出处
期刊:Seminars in Diagnostic Pathology [Elsevier BV]
卷期号:38 (6): 193-198 被引量:8
标识
DOI:10.1053/j.semdp.2020.12.001
摘要

Cancer of unknown primary (CUP) refers to metastatic tumors for which the primary tumor of origin cannot be determined at the time of diagnosis, despite extensive clinicopathologic investigations. Molecular profiling is increasingly able to predict a probable primary tumor type for CUP when clinicopathologic workup is inconclusive. Numerous studies have explored the use of various molecular profiling techniques for identification of site/tissue of origin of CUP. These techniques include gene expression profiling utilizing microarray, reverse transcriptase polymerase chain reaction, RNA-sequencing, somatic gene mutation profiling with next-generation DNA sequencing, and epigenomics including DNA methylation profiling. Despite the generally poor prognosis of CUP, a minority of patients can expect to benefit from targeted therapy despite being agnostic to the tissue of origin. Studies have explored the use of various molecular profiling techniques to predict prognostic and therapeutic biomarkers, with the goal of improving outcome for patients with CUP. However, discordant results between non-randomized and randomized clinical trials in evaluating tumor-type specific therapies raise uncertainties of the benefits of molecularly-predicted tissue of origin-based treatment in routine clinical use. Nevertheless, the current overall trend is in favor of using molecular tools to refine the diagnosis and clinical management of patients with CUP. More large-cohort, randomized prospective studies are needed to assess and validate the utility and feasibility of molecular profiling to uncover potentially targetable genetic alterations. These efforts will also yield further biological insights into the biology and pathogenesis of CUP (Graphical Abstract).
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