Germline RAD54L with somatic POLE defect implicated in Hypermutation phenotype: case report

Background Colorectal cancer is one of the most frequent causes of death among cancer patients. Hypermutated CRC is an extraordinary case of cancer, but curable if detected at early stages. However, the mechanism for developing a hypermutated CRC remains unclear. An association between RAD54L germline mutation and POLE exonuclease domain hypermutated cancer has not been reported before. Case presentation We present a rare case of a 41-year-old Chinese female with a right-sided colon adenocarcinoma who harboured a (p.P286R) POLE somatic mutation. Genomic analysis was performed using the Illumina HiSeq Sequencing platform, which, identified MSS tumour with a (c.1093_1169 + 15dup) germline mutation in RAD54L gene and tumour mutation burden of 377.0 Muts/Mb. Based on our report a new mechanism for developing hypermutated colon cancer has been conjectured through a novel RAD54L_POLE DSBR pathway. Conclusion This report highlights the clinical importance of next-generation sequencing technology in diagnosing rare tumours and investigating novel mechanisms for developing exceptional genetic diseases.