进展期乳腺癌中转移部位的遗传变异频率存在差异。
Frequency of genetic alterations differs in advanced breast cancer between metastatic sites.
发表日期：2023 Sep 06
作者：
Isabel Grote, Alexandra Poppe, Ulrich Lehmann, Matthias Christgen, Hans Kreipe, Stephan Bartels
来源：
Brain Structure & Function
摘要：
大约20%-30%的乳腺癌（BC）患者会发展成远处转移，首选点位是骨骼、肝脏、肺部和脑部。不同内在亚型的BC偏好不同的转移部位。这些亚型在遗传突变丰度方面存在差异，可能会影响转移的定位。目前，关于BC转移部位与突变谱之间的关系的信息有限。在本研究中，通过NGS和热原测序，调查了n=521例BC转移性灶在最常累及的部位（骨骼、脑、肝脏和肺）中AKT1、ERBB2、ESR1、PIK3CA和TP53突变的频率。在这些病例中，64%存在体细胞突变。PIK3CA和TP53是研究中突变最常见的基因。我们提供了BC突变谱与受影响转移部位的分析。根据转移部位所影响的器官，遗传突变存在显著差异。TP53突变主要出现在脑转移（51.0%）中，脑外转移中TP53突变样本的比例较低。PIK3CA突变在肝脏（40.6%）、肺部（36.8%）和骨骼转移（35.7%）中频繁出现，而在脑部转移中较不常见（18.4%）。ESR1突变的最高百分比出现在肝脏和肺部转移中（各约30%），而脑部转移中ESR1突变显著较少，仅有2.0%的病例。总之，我们发现BC的突变状态在转移到的器官和内在亚型之间存在显著差异。转移性癌症的器官趋势可能受到个体BC突变谱的影响。© 2023 The Authors. Genes, Chromosomes and Cancer published by Wiley Periodicals LLC.
About 20%-30% of breast cancer (BC) patients will develop distant metastases, preferentially in bones, liver, lung, and brain. BCs with different intrinsic subtypes prefer different sites for metastasis. These subtypes vary in the abundance of genetic alterations which may influence the localization of metastases. Currently, information about the relation between metastatic site and mutational profile of BC is limited. In this study, n = 521 BC metastases of the most frequently affected sites (bone, brain, liver, and lung) were investigated for the frequency of AKT1, ERBB2, ESR1, PIK3CA, and TP53 mutations via NGS and pyrosequencing. Somatic mutations were present in 64% cases. PIK3CA and TP53 were the most frequently mutated genes under study. We provide an analysis of the mutational profile of BCs and the affected metastatic site. Genetic alterations differed significantly depending on the organ site affected by metastases. TP53 mutations were mostly observed in brain metastases (51.0%), metastases outside of the brain revealed a much lower proportion of TP53 mutated samples. PIK3CA mutations are frequent in liver (40.6%), lung (36.8%), and bone metastases (35.7%), whereas less common in brain metastases (18.4%). The highest percentage of ESR1 mutations was observed in liver and lung metastases (about 30% each), whereas metastatic lesions in the brain showed significantly less ESR1 mutations, only in 2.0% of the cases. In summary, we found significant differences of mutational status in mBC depending on the affected organ and intrinsic subtype. Organotropism of metastatic cancer spread may be influenced by the mutational profile of individual BCs.© 2023 The Authors. Genes, Chromosomes and Cancer published by Wiley Periodicals LLC.