Citations 2
Circulating tumour DNA reveals genetic traits of patients with intraductal carcinoma of the prostate
Zhao, Jinge , Sun, Guangxi , Dai, Jindong, Chen, Junru , Zhang, Mengni , Ni, Yuchao , Shen, Pengfei , Zhao, Xiaochen , Zhang, Bei , Pan, Xiuyi , Yin, Xiaoxue , Liang, Jiayu, Wang, Zhipeng , Liao, Banghua , Liu, Zhenhua , Armstrong, Cameron M. , Chen, Ni , Zeng, Hao , Wang, Zhipeng , Zeng, Hao , Chen, Junru , Wang, Zhipeng , Zhu, Sha , Zhang, Haoran , Nie, Ling , Zhang, Xingming , Zhu, Xudong , Gao, Allen C , Huang, Haojie
BJU International | June 29, 2021 | Volume: 129 | Issue: 3 | Pages: 345-355
Objectives To investigate the genetic alterations of patients with prostate cancer (PCa) with and without intraductal carcinoma of the prostate (IDC‐P). Patients and Methods We performed targeted sequencing of plasma cell‐free DNA on 161 patients with prostate adenocarcinoma (PAC) with IDC‐P and 84 without IDC‐P. Genomic alterations were compared between these two groups. The association between genetic alterations and patients’ survival outcomes was also explored. Results We identified that 29.8% (48/161) and 21.4% (18/84) of patients with and without IDC‐P harboured genomic alterations in DNA repair pathways, respectively ( P = 0.210). Pathogenic germline DNA repair alterations were frequently detected in IDC‐P carriers compared to IDC‐P non‐carriers (11.8% [19/161] vs 2.4% [two of 84], P = 0.024). Germline BReast CAncer type 2 susceptibility protein ( BRCA2 ) and somatic cyclin‐dependent kinase 12 ( CDK12 ) defects were specifically identified in IDC‐P carriers relative to PAC ( BRCA2 : 8.7% [14/161] vs 0% and CDK12 : 6.8% [11/161] vs 1.2% [one of 84]). Patients with IDC‐P had a distinct androgen receptor (AR) pathway alteration, characterised by an enrichment of nuclear receptor corepressor 2 ( NCOR2 ) mutations compared with patients with pure PAC (21.1% [34/161] vs 6.0% [five of 84], P = 0.004). Increased AR alterations were detected in patients harbouring tumours with an IDC‐P proportion of ≥10% vs those with an IDC‐P proportion of <10% (6.4% [five of 78] vs 18.1% [15/83], P = 0.045). For IDC‐P carriers, tumour protein p53 ( TP53 ) mutation was associated with shorter castration‐resistant‐free survival (median 10.9 vs 28.9 months, P = 0.026), and BRCA2 alteration was related to rapid prostate‐specific antigen progression for those receiving abiraterone treatment (median 9.1 vs 11.9 months, P = 0.036). Conclusion Our findings provide genomic evidence explaining the aggressive phenotype of tumours with IDC‐P, highlighting the potential therapeutic strategies for this patient population.
Integrated exome and RNA sequencing of TFE3-translocation renal cell carcinoma
Sun, Guangxi , Liang, Jiayu, Yin, Xiaoxue , Zhang, Mengni , Yao, Jin , He, Ning , Armstrong, Cameron M. , Zheng, Linmao , Sun, Xiaomeng , Yang, Xiaoxia , Zhao, Wanbin , Liao, Banghua , Pan, Xiuyi , Yang, Ling , Zhao, Jinge , Dai, Jindong, Shen, Yali , Huang, Rui , Liu, Jiandong , Wang, Zhipeng , Ni, Yuchao , Wei, Qiang , Zhou, Qiao , Liu, Zhenhua , Shen, Pengfei , Chen, Ni , Zeng, Hao , Sun, Guangxi , Chen, Junru , Zhang, Xingming , Zhu, Sha , Nie, Ling , Chen, Yahong , Zhang, Haoran , Liu, Jiyan , Li, Xiang , Huang, Haojie
No container title available | March 11, 2021 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract TFE3-translocation renal cell carcinoma (TFE3-tRCC) is a rare and heterogeneous subtype of kidney cancer that has no standard treatment for advanced disease. We described comprehensive molecular characteristics of 63 untreated primary TFE3-tRCCs based on whole-exome and RNA sequencing. TFE3-tRCC is highly heterogeneous, both clinicopathologically and genotypically. ASPSCR1-TFE3 fusion, certain fusion isoforms and high somatic copy number alteration burdens were associated with aggressive features and poor outcomes. Apart from tumors with MED15-TFE3 fusion, most TFE3-tRCCs exhibited low PD-L1 expression and low T-cell infiltration. Unsupervised transcriptomic analysis revealed five molecular clusters with distinct angiogenesis, stroma, proliferation and KRAS down signatures, which showed association with fusion patterns and prognosis. Specifically, the high angiogenesis/stroma/proliferation cluster exclusively consisted of tumors with ASPSCR1-TFE3 fusion, which was likely to benefit from combination of immune checkpoint and anti-angiogenesis inhibitors. Our findings reveal the genomic and transcriptomic features of TFE3-tRCC and provide insights into precision medicine for this disease.