Association of gliomas and BRCA 1 germline mutation: A possible linkage.

Abstract

e12502 Background: Gliomas are known to occur in association with several well-defined hereditary tumor syndromes such as NF1 and NF2, tuberous sclerosis, Li Fraumeni syndrom and Turcot syndrome. In addition, familial clustering of glioma in absence of these tumor syndrome have also been described. Methods: We have already reported the case of a 35 years old man who was diagnosed with an oligodendroglioma. Familial history reported 3 ovarian cancers at the first degree. Genetic testing had shown the BRCA1 exonic deletion c.3819del GTAAA, p. 1241 ter. (Patient 1 ) We collected 2 more cases of patients diagnosed with glioma and carrying BRCA1 mutation, whom have been seen by other physicians in an other hospital. Results: The second patient is a 59-year-old woman diagnosed with a glioblastoma with important oligodendroglioma differenciation (Patient 2). She was 43 at the time of diagnosis. At the age of 54, she developed a bilateral breast cancer. Moreover, the pedigree revealed a familial history of 4 breast cancers at the first degree. Genetic testing had shown the BRCA1 exonic substitution c.181T>G, p.Cys61Gly. The third patient is a 40-year -old woman diagnosed with an intra medullar pilocytic astrocytoma (Patient 3). This tumour is not usual which allows to keep in mind the genetic procedure. Beforehand, she had been diagnosed with a breast cancer at the age of 36. The pedigree revealed 6 breast cancers among the family and thus, BRCA analysis had been performed and showed the BRCA 1 exonic substitution c.3403 C>T, p.Gln 1135 X. Consequently, the patient had a prophylactic ovarian surgery at the age of 37 and contralateral prophylactic mastectomy at the age of 40. Interestingly, P1 had a BRCA1 deletion whereas P2 and P3 had BRCA1 substitution. On the other hand, P1 and P3 had Exon 11 mutation that both resulted in a truncated protein. Whereas, P2 had an exon 5 missens mutation. Conclusions: No specific association has been reported between BRCA1 mutation and glial tumor occurrence. These cases point out a possible relationship between BRCA1 germline mutation and glioma occurrence such as the relevance of familial history screening in glioma patients. Further investigations are needed to identify a disease-causing locus by genetic linkage analysis.