Abstract
BackgroundColorectal 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 presentationWe 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.ConclusionThis report highlights the clinical importance of next-generation sequencing technology in diagnosing rare tumours and investigating novel mechanisms for developing exceptional genetic diseases.
Highlights
Colorectal cancer is one of the most frequent causes of death among cancer patients
This report highlights the clinical importance of next-generation sequencing technology in diagnosing rare tumours and investigating novel mechanisms for developing exceptional genetic diseases
The main causes of the mutations that accumulate in hypermutated Colorectal cancer (CRC) are mismatch repair (MMR) defects and somatic alterations in the exonuclease domain of DNA polymerase epsilon (POLE) [4]
Summary
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. Hypermutated colon cancer was defined as a tumour with a somatic mutation rate > 12 per megabases and had a median of 728 non-silent mutations [2]. The main causes of the mutations that accumulate in hypermutated CRC are mismatch repair (MMR) defects and somatic alterations in the exonuclease domain of DNA polymerase epsilon (POLE) [4]. A POLE colorectal tumour tends to be microsatellite stable (MSS), occur during early-onset cancer (before 50 years age) and be located predominantly in the right colon [5].
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