Understanding the mechanisms underlying the malignant progression of cancer cells is crucial for early diagnosis and therapeutic treatment for cancer. Mutational heterogeneity of breast cancer suggests that about a dozen of cancer genes consistently mutate, together with many other genes mutating occasionally, in patients. Using the whole-exome sequences and clinical information of 468 patients in the TCGA project data portal, we analyzed mutated protein domains and signaling pathway alterations in order to understand how infrequent mutations contribute aggregately to tumor progression in different stages. Our findings suggest that while the spectrum of mutated domains was diverse, mutations were aggregated in Pkinase, Pkinase Tyr, Y-Phosphatase and Src-homology 2 domains, highlighting the genetic heterogeneity in activating the protein tyrosine kinase signaling pathways in invasive ductal breast cancer. The study provides new clues to the functional role of infrequent mutations in protein domain regions in different stages for invasive ductal breast cancer, yielding biological insights into metastasis for invasive ductal breast cancer.

中文翻译：

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浸润性导管乳腺癌的阶段特异性蛋白域突变谱

了解癌细胞恶性进展的机制对于癌症的早期诊断和治疗至关重要。乳腺癌的突变异质性表明，患者体内大约有十几个癌症基因持续突变，还有许多其他基因偶尔突变。利用 TCGA 项目数据门户中 468 名患者的全外显子组序列和临床信息，我们分析了突变的蛋白结构域和信号通路的变化，以了解罕见突变如何共同促进不同阶段的肿瘤进展。我们的研究结果表明，虽然突变结构域的范围多种多样，但突变聚集在 Pkinase、Pkinase Tyr、Y-磷酸酶和 Src-homology 2 结构域中，突显了浸润性导管乳腺癌中蛋白酪氨酸激酶信号通路激活的遗传异质性。该研究为浸润性导管乳腺癌不同阶段蛋白质结构域区域的罕见突变的功能作用提供了新的线索，从而为浸润性导管乳腺癌的转移提供了生物学见解。