内含子多腺苷酸化（IPA）是指一种特定类型的替代多腺苷酸化，其中基因利用位于其内含子内的多腺苷酸化位点。在各种类型的癌症中都观察到了异常的 IPA 事件。 IPA 可以产生非编码转录本或截短的蛋白质编码转录本，在所得蛋白质产物中编码序列发生改变。因此，IPA 事件有可能充当肿瘤新抗原的储存库。在这里，我们开发了一种称为 DIPAN 的计算方法，它结合了 IPA 检测、蛋白质片段化和 MHC 结合预测来预测 IPA 衍生的新抗原。利用乳腺癌细胞系和卵巢癌临床样本的 RNA-seq，我们证明了 IPA 事件对新抗原库的重大贡献。通过质谱免疫肽组分析，我们进一步阐明了IPA衍生的新抗原在癌细胞表面的加工和呈递。虽然大多数 IPA 衍生的新抗原是样本特异性的，但在癌细胞系和临床样本中都发现了共享的新抗原。此外，我们证明了 IPA 衍生的新抗原负荷与癌症患者的总体生存率之间存在关联。© 2024 作者。

Intronic polyadenylation (IPA) refers to a particular type of alternative polyadenylation where a gene makes use of a polyadenylation site located within its introns. Aberrant IPA events have been observed in various types of cancer. IPA can produce noncoding transcripts or truncated protein-coding transcripts with altered coding sequences in the resulting protein product. Therefore, IPA events hold the potential to act as a reservoir of tumor neoantigens. Here, we developed a computational method termed DIPAN, which incorporates IPA detection, protein fragmentation, and MHC binding prediction to predict IPA-derived neoantigens. Utilizing RNA-seq from breast cancer cell lines and ovarian cancer clinical samples, we demonstrated the significant contribution of IPA events to the neoantigen repertoire. Through mass spectrometry immunopeptidome analysis, we further illustrated the processing and presentation of IPA-derived neoantigens on the surface of cancer cells. While most IPA-derived neoantigens are sample-specific, shared neoantigens were identified in both cancer cell lines and clinical samples. Furthermore, we demonstrated an association between IPA-derived neoantigen burden and overall survival in cancer patients.© 2024 The Authors.