Studies reveal aristolochic acid mutation characteristics can be used to identify low-risk subtypes of upper urinary tract urothelial cancer

Recently, Ci Weimin research group of Beijing genome research institute (national biological information center) of Chinese academy of sciences cooperate with Zhou Liqun group of first hospital of Peking university, It is revealed that the molecular typing of single nucleotide mutation and aristolochic acid (AA)-related mutation can be used as molecular markers to screen low-risk subtypes of upper urinary tract epithelial carcinoma and have the potential to realize non-invasive detection. The research results are based on Aristolochic acid mutational signature definitions the low-risk subtype in upper tract urothelial carcinoma   The topic is in the academic journal Theranostics   Published online.

Urinary tract epithelial cancer is one of the most common malignant tumors of urinary system, of which about 90%-95% occur in bladder and only 5%-10% in upper urinary tract urothelial cancer (UTUC). However, in East Asia, due to the popularity of Chinese herbal medicines, UTUC accounts for up to 30%. Some studies have confirmed that AA exposure is the main reason for the high incidence of UTUC and Chinese herbal medicine nephropathy. The purpose of this study is to explore the clinical molecular characteristics and potential diagnosis and treatment ideas of UTUC in China. Researchers sequenced the entire genome of 90 UTUC samples, All samples were clustered according to the analyzed mutation characteristics of the tumor somatic mutations in Cancer (Catalogue of Somatic Mutations in Cancer), UTUC patients with a high proportion of AA mutation (signature 22) (i.e. AA Sig subgroup) have a higher proportion of AA Chinese herbal medicine exposure. The proportion of female patients in this subgroup is high, and they often show multiple lesions and poor renal function. However, survival analysis shows that patients with AA Sig subgroup have better prognosis than those with a low proportion of signature 22 (No-AA Sig). Multi-sample genomic association analysis of AA Sig subgroup multifocal patients speculates that regional cancerization and luminal implantation may jointly promote multifocal tumor and bladder recurrence in this subgroup of patients. In addition, AA Sig subclass tumors show a high mutation load, predicting the number of tumor antigens and immune cell infiltration, suggesting that AA Sig subclass patients may be a potential population for tumor immunotherapy. Finally, the study found that AA Sig subtype can still be predicted in urine supernatant cell free DNA (cfDNA) by using low-level whole genome sequencing. The above results show that AA Sig is a low-risk tumor type and has the potential to realize early diagnosis and monitoring through mutation detection in urine.

The research was supported by funds such as the Strategic Pilot Science and Technology Project of the Chinese Academy of Sciences, the National Natural Science and the National Key Research and Development Plan.


Aristolochic acid (AA) mutation features are used as a screening tool to identify low-risk UTUC subclasses with therapeutic significance.