Interfocal heterogeneity challenges the clinical usefulness of molecular classification of primary prostate cancer
Interfocal heterogeneity challenges the clinical usefulness of molecular classification of primary prostate cancer
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DOI：
10.1038/s41598-019-49964-7
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发表时间：
2019-09-19
影响因子：
4.6
通讯作者：
Lovf, Marthe
中科院分区：
文献类型：
--
作者：
Carm, Kristina Totland;Hoff, Andreas M.;Lovf, Marthe
前列腺癌是一种高度异质性的疾病，通常在初步诊断时存在多个不同的癌灶。前列腺癌的分子分类可能有助于诊断和治疗的精确性。癌症基因组图谱（TCGA）发表了一个有前途的基因组分类器，成功地将74%的原发性前列腺癌分为七组，基于每个患者的一个癌症样本。在这里，我们探索这种分类的临床实用性，通过测试分类器的性能在多焦点的情况下。我们分析了来自39名患者的85个不同癌症病灶的106个癌症样本。通过来自全外显子组测序和靶向定性和定量基因表达测定的体细胞突变数据，31%的患者被唯一地分类为七个TCGA类别之一。此外，来自同一病灶的不同样本在12%的病灶中具有冲突的分类。总之，病灶内和病灶间异质性的水平是广泛的，必须考虑到在临床上有用的原发性前列腺癌的分子分类的发展。
Prostate cancer is a highly heterogeneous disease and typically multiple distinct cancer foci are present at primary diagnosis. Molecular classification of prostate cancer can potentially aid the precision of diagnosis and treatment. A promising genomic classifier was published by The Cancer Genome Atlas (TCGA), successfully classifying 74% of primary prostate cancers into seven groups based on one cancer sample per patient. Here, we explore the clinical usefulness of this classification by testing the classifier's performance in a multifocal context. We analyzed 106 cancer samples from 85 distinct cancer foci within 39 patients. By somatic mutation data from whole-exome sequencing and targeted qualitative and quantitative gene expression assays, 31% of the patients were uniquely classified into one of the seven TCGA classes. Further, different samples from the same focus had conflicting classification in 12% of the foci. In conclusion, the level of both intra- and interfocal heterogeneity is extensive and must be taken into consideration in the development of clinically useful molecular classification of primary prostate cancer.