Abstract
RATIONALE: PMS1 is one of the mismatch repair (MMR) genes with potential crucial roles in carcinogenesis. Very few reports have been identified on germline PMS1 mutations with definite disease phenotype. Here we report a case of hepatocellular carcinoma (HCC) with a novel potential pathogenic germline PMS1 mutation. PATIENT CONCERNS: A 46-year-old Chinese male with Hepatitis B infection history presented a single cancerous nodule (10×12×10 mm) at the left lobe of liver. The nodule was considered malignant by type-B ultrasonic and computed tomography (CT) examinations. DIAGNOSIS AND INTERVENTION: Liver lobectomy was performed to remove the liver cancerous nodule and postoperative TACE was performed for recurrence prevention. Pathological examination on resected tumor tissue confirmed the diagnosis of HCC. Whole-exome sequencing (WES) identified the c.900delT (p.D300fs) heterozygous germline mutation of PMS1, along with 253 nonsynonymous single nucleotide variations (SNVs), 14 Insertion or deletion mutations (INDELs) and 21 genes with copy number variations (CNVs). Three-dimensional prediction of protein tertiary structure suggested that the conformation of the enzyme active site and the ligand binding site might be changed due to the protein truncation. OUTCOMES: The patient was still alive in good condition with no sign of recurrence in 12 months follow-up period. LESSONS: The affected pathways in this case were unique from previously reported HCC patients with no PMS1 germline mutations. The novel PMS1 germline mutation may increase cancer risk. The roles of PMS1 germline mutations in carcinogenesis need further investigation.