Exploring the Role of the Gene in Breast, Ovarian and Endometrial Cancer.

BACKGROUND

germline monoallelic variants have been detected in a number of patients affected by breast/ovarian cancer or endometrial cancer, suggesting a potential susceptibility role, though their significance remains elusive since the disease mechanism is normally recessive. Hence, the aim of this research was to explore the hypothesis that a second hit could have arisen in the other allele in the tumor tissue.

METHODS

we used Sanger sequencing and immunohistochemistry to search for a second variant in the tumoral DNA and to assess protein expression, respectively.

RESULTS

we detected one variant of unknown significance, one variant with conflicting interpretation of pathogenicity and three benign/likely benign variants; the protein was not detected in the tumor tissue of half of the patients, and in others, its expression was reduced.

CONCLUSIONS

our results fail to demonstrate that germinal monoallelic variants increase cancer risk through a LOH (loss of heterozygosity) mechanism in the somatic tissue; however, the absence or partial loss of the protein in many tumors suggests its dysregulation regardless of genetic status.