Increased Incidence of Choroid Plexus Carcinoma Due to the Germline TP53 R337H Mutation in Southern Brazil

Abstract

BackgroundChoroid plexus carcinomas (CPC) are rare tumors predominantly found in children. Given the high frequency of the germline R337H mutation in the TP53 gene in southern Brazil, we have evaluated the frequency of the R337H mutation in families with CPC in children.Methodology/Principal FindingsThe present series included 29 patients that were admitted to the same institution from 1992 to 2010, including 22 children with CPC (0.08–13.6 years of age at diagnosis) and 7 children with papilloma of the choroid plexus (Pp; 0.5–9.8 years of age). Surgical resection was possible in 28 children. Blood and/or tumor DNA was extracted and analyzed using PCR-RFLP and results were confirmed by sequencing 240 bp of the TP53 exon 10. The patients, all parents, and some relatives submitted samples for blood DNA analysis. In addition, we have also examined the presence of the mutation in DNA from paraffin-embedded tumor samples to evaluate loss of heterozygosity. We found 63.3% (14/22) of the CPC patients positive for the germline R337H mutation; CPC samples were either heterozygous (n = 7), lost only the wild-type (n = 4), or only the R337H copy (n = 2). One CPC sample was not available. All Pp cases (7/7, 100%) were negative for R337H. Cure (>5 years survival free of disease) was observed in 18.1% of the CPC cases with the R337H mutation (2/11), 71.4% of the Pp (5/7), and 25% of CPC cases negative for the R337H mutation (2/8). Family history of cancer (with 2 or more cancer cases) was exclusively identified on the parental side segregating the R337H mutation, and 50% (7/14) of them were compatible with Li-Fraumeni-like syndrome.SignificanceOur results show for the first time that the R337H TP53 mutation is responsible for 63% of the CPC cases in children, suggesting a higher incidence of CPC in southern Brazil.

Towards an understanding of the role of p53 in adrenocortical carcinogenesis

“…Initially, the R337H mutation was thought to predispose carriers primarily to ACC; however, recently it has been identified in association with families meeting criteria for LFL (Li Fraumeni-like syndrome)(Achatz, Olivier, Le Calvez et al, 2007) as well as with individuals with breast cancer(Assumpcao, Seidinger, Mastellaro et al, 2008,Palmero, Schuler-Faccini, Caleffi et al, 2008), choroid plexus carcinoma and osteosarcoma(Custodio, Taques, Figueiredo et al, 2011,Seidinger, Mastellaro, Paschoal Fortes et al, 2011). Nevertheless, ACC constitutes the plurality of tumors identified in carriers of the R337H allele(Petitjean et al, 2007).…”

Impact of Early Postnatal Androgen Exposure on Voice Development

“…Nevertheless, the foremost research goal–determination of the impact of androgen exposure leading to the development of remarkable pre-pubertal virilizing signs on long-term (adult or adolescent) female F0–was achieved. All the subjects (19/19) demonstrated a good understanding of ACT signs and symptoms, especially due to their participation in previous studies [12], [13], [32]. The variables of dose, timing, and duration of androgen exposure were all found to be determinants of virilization in the subjects, of whom 18 had experienced virilization during the pre-pubertal stage and 1 during puberty.…”

Surgical outcomes in choroid plexus papillomas: an institutional experience

“…Furthermore, we have demonstrated that these tumors can be safely removed, regardless of location, and likely do not require up-front radiation, even in cases of STR. Since some CPPs still recur despite GTR, future studies should build upon previously published genetic analysis of these tumors in order to identify markers that can refine our current grading scheme and provide improved insight towards predicting which tumors will recur [22][23][24][25][26]. Platelet-derived growth factor receptor (PDGFR) has been implicated in choroid plexus tumors, particularly carcinomas [27].…”