AUTHOR=Yang Zhen , Cui Wei , Yu Ruoying , Dong Xinhua , Zhao Jian , Dai Lu , Ou Qiuxiang , Bao Hua , Wu Xue , Wu Chuanxin , Lai Jinhuo
TITLE=Altered Signaling Pathways Revealed by Comprehensive Genomic Profiling in Patients With Unknown Primary Tumors
JOURNAL=Frontiers in Oncology
VOLUME=12
YEAR=2022
URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.753311
DOI=10.3389/fonc.2022.753311
ISSN=2234-943X
ABSTRACT=PurposeCarcinoma of unknown primary (CUP) is a clinically aggressive disorder with early tumor dissemination. Identifying molecular traits of CUP can be not only beneficial for a better therapeutic approach but also potentially valuable for patients with general metastatic dissemination.
Patients and MethodsWe retrospectively investigated a total of 35 unique CUP cases. Tumor tissue samples were available in 26 patients, and plasma samples were available in 22 patients. Targeted sequencing was performed with a panel of 416 pan cancer-related genes.
ResultsA genomic landscape of the CUP cohort showed that TP53 mutation was the most frequently observed mutation while MYC amplification was the most common CNV. Aberrant TP53, RTK-RAS, and PI3K signaling pathways were also prevalent, identified in more than half of the cases with tumor tissue. Around 58% of the CUP cases harbored homologous recombinant repair (HRR) pathway gene alterations. The tumor mutational load of CUP patients with altered HRR pathway displayed a significant increase than that of patients with intact HRR. Clinically actionable mutations were identified in eight patients, which may benefit from targeted therapies. Eight patients were treated with platinum-based chemotherapy, showing different responses, HRR, and LOH status.
ConclusionCollectively, our data have provided much-need insights into the treatment options for patients diagnosed with CUP in the era of precision medicine.