Abstract：
BACKGROUND: Recurrent intestinal-type sinonasal adenocarcinoma (ITAC) can occur several years after primary treatment and with different histology. We aimed to clarify if such recurrences could be second primary tumors and to identify actionable mutations as targets for personalized treatment of recurrent ITAC.
METHODS: Twelve pairs of primary and recurrent ITAC were histologically examined and analyzed by next-generation sequencing.
RESULTS: Histological differences between primary and recurrent tumor pairs were observed in five cases. Frequent mutations included TP53, APC, TSC2, ATM, EPHA2, BRCA2, LRP1B, KRAS, and KMT2B. There was 86% concordance of somatic mutations between the tumor pairs, while four cases carried additional mutations in the recurrence.
CONCLUSIONS: We found all cases to be clonal recurrences and not second primary tumors. Moreover, tumor pairs showed a remarkable genomic stability, suggesting that personalized treatment of a recurrence may be based on actionable molecular genetic targets observed in the primary tumor.
METHODS: Twelve pairs of primary and recurrent ITAC were histologically examined and analyzed by next-generation sequencing.
RESULTS: Histological differences between primary and recurrent tumor pairs were observed in five cases. Frequent mutations included TP53, APC, TSC2, ATM, EPHA2, BRCA2, LRP1B, KRAS, and KMT2B. There was 86% concordance of somatic mutations between the tumor pairs, while four cases carried additional mutations in the recurrence.
CONCLUSIONS: We found all cases to be clonal recurrences and not second primary tumors. Moreover, tumor pairs showed a remarkable genomic stability, suggesting that personalized treatment of a recurrence may be based on actionable molecular genetic targets observed in the primary tumor.
摘要：
背景：复发性肠型鼻窦腺癌（ITAC）可在初次治疗后数年发生，且组织学不同。我们旨在阐明此类复发是否可能是第二原发肿瘤，并确定可操作的突变作为复发性ITAC个性化治疗的靶标。
方法：对12对原发性和复发性ITAC进行组织学检查和下一代测序分析。
结果：在5例中观察到原发性和复发性肿瘤对之间的组织学差异。频繁的突变包括TP53，APC，TSC2,ATM,EPHA2,BRCA2,LRP1B,KRAS,KMT2B肿瘤对之间的体细胞突变有86％的一致性，而4例病例在复发中携带了额外的突变。
结论：我们发现所有病例均为克隆性复发，而非第二原发肿瘤。此外，肿瘤对显示出显著的基因组稳定性，提示复发的个性化治疗可能基于在原发肿瘤中观察到的可操作的分子遗传靶标。
方法：对12对原发性和复发性ITAC进行组织学检查和下一代测序分析。
结果：在5例中观察到原发性和复发性肿瘤对之间的组织学差异。频繁的突变包括TP53，APC，TSC2,ATM,EPHA2,BRCA2,LRP1B,KRAS,KMT2B肿瘤对之间的体细胞突变有86％的一致性，而4例病例在复发中携带了额外的突变。
结论：我们发现所有病例均为克隆性复发，而非第二原发肿瘤。此外，肿瘤对显示出显著的基因组稳定性，提示复发的个性化治疗可能基于在原发肿瘤中观察到的可操作的分子遗传靶标。
