PMS2 Novel Mutation In Breast Cancer: A Case Report

Background: Breast cancer is the second most commonly diagnosed cancer in women. In many casesof familial breast cancer the genetic basis for the disease and the mechanism of inheritance areunclear. Breast cancer from mismatch repair (MMR) gene mutation carriers resembles commonbreast carcinoma in many respects. The PMS2 gene encodes a protein that plays an important rolein repairing DNA. Detection of germline mutation in PMS2 is significantly complicated by thepresence of numerous pseudogenes. Methods and Results: We present a woman with familial breastcancer. The pedigree showed the same cases in three generation. Using whole exome sequencingthe heterozygous variant c.2350G> A (p.Asp784Asn) on gene PMS2 gene has been found. To validatethis novel mutation in probands’ healthy daughter, we used a modified long-range PCR method toevaluate PMS2, thus pseudogene interference has beed avoided. Sanger sequencing of PMS2 geneshowed no mutation in her daughter. Conclusion: This novel mutation has not been reported before.The clinical outcome of PMS2 germline mutations are poorly understood compared with other MMRgene mutations. The frequency of this mutation in normal population is very low. Bioinformaticanalysis of the mutation by PolyPhen2 and SIFT showed that the protein will be damaged. Thisamino acid change (Asp to Asn) may affect the function of PMS2.