RESUMEN
The nuclease MRE11A is often included in genetic test panels for hereditary breast and ovarian cancer (HBOC) due to its BRCA1-related molecular function in the DNA repair pathway. However, whether MRE11A is a true predisposition gene for HBOC is still questionable. We determined to investigate this notion by dissecting the molecular genetics of the c.1516G > T;p.E506* truncating MRE11A variant, that we pinpointed in two unrelated French-Canadian (FC) HBOC patients. We performed a case-control study for the variant in ~ 2500 breast, ovarian, and endometrial cancer patients from the founder FC population of Quebec. Furthermore, we looked for the presence of second somatic alterations in the MRE11A gene in the tumors of the carriers. In summary, these investigations suggested that the identified variant is not associated with an increased risk of developing breast or ovarian cancer. We finally performed a systematic review for all the previously reported MRE11A variants in breast and ovarian cancer. We found that MRE11A germline variants annotated as pathogenic on ClinVar often lacked evidence for such classification, hence misleading the clinical management for affected patients. In summary, our report suggests the lack of clinical utility of MRE11A testing in HBOC, at least in the White/Caucasian populations.
Asunto(s)
Neoplasias de la Mama/genética , Predisposición Genética a la Enfermedad , Proteína Homóloga de MRE11/genética , Mutación , Neoplasias Ováricas/genética , Adulto , Alelos , Neoplasias de la Mama/diagnóstico , Análisis Mutacional de ADN , Femenino , Mutación de Línea Germinal , Síndrome de Cáncer de Mama y Ovario Hereditario/genética , Humanos , Proteína Homóloga de MRE11/metabolismo , Neoplasias Ováricas/diagnóstico , Linaje , Quebec , Secuenciación del ExomaRESUMEN
An etiological role for human papilloma viruses (HPVs) has been proposed for a variety of malignancies, and especially in cervical carcinomas. The role of HPVs in prostate cancer remains controversial. In particular, using primers derived from the L1 gene of HPV, it has been suggested that HPV sequences are associated with prostate malignancies. PCR and Southern blot hybridization was used to detect the presence of HPV DNA in fresh tissue from patients undergoing radical prostatectomy for prostate cancer. In total, 40 individual patients were analyzed and none of the samples contained detectable HPV DNA sequences.