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BMC Cancer
Published in: BMC Cancer 1/2008

Open Access 01-12-2008 | Research article

Association of the germline TP53R337H mutation with breast cancer in southern Brazil

Authors: Juliana G Assumpção, Ana Luíza Seidinger, Maria José Mastellaro, Raul C Ribeiro, Gerard P Zambetti, Ramapriya Ganti, Kumar Srivastava, Sheila Shurtleff, Deqing Pei, Luiz Carlos Zeferino, Rozany M Dufloth, Silvia Regina Brandalise, José Andres Yunes

Published in: BMC Cancer | Issue 1/2008

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Abstract

Background

The germline TP53-R337H mutation is strongly associated with pediatric adrenocortical tumors (ACT) in southern Brazil; it has low penetrance and limited tissue specificity in most families and therefore is not associated with Li-Fraumeni syndrome. However, other tumor types, mainly breast cancer, have been observed in carriers of several unrelated kindreds, raising the possibility that the R337H mutation may also contribute to breast tumorigenesis in a genetic background-specific context.

Methods

We conducted a case-control study to determine the prevalence of the R337H mutation by sequencing TP53 exon 10 in 123 women with breast cancer and 223 age- and sex-matched control subjects from southern Brazil. Fisher's test was used to compare the prevalence of the R337H.

Results

The R337H mutation was found in three patients but in none of the controls (p = 0.0442). Among the carriers, two had familial history of cancer meeting the Li-Fraumeni-like criteria. Remarkably, tumors in each of these three cases underwent loss of heterozygosity by eliminating the mutant TP53 allele rather than the wild-type allele. Polymorphisms were identified within the TP53 (R72P and Ins16) and MDM2 (SNP309) genes that may further diminish TP53 tumor suppressor activity.

Conclusion

These results demonstrate that the R337H mutation can significantly increase the risk of breast cancer in carriers, which likely depends on additional cooperating genetic factors. These findings are also important for understanding how low-penetrant mutant TP53 alleles can differentially influence tumor susceptibility.
Appendix
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Metadata
Title
Association of the germline TP53R337H mutation with breast cancer in southern Brazil
Authors
Juliana G Assumpção
Ana Luíza Seidinger
Maria José Mastellaro
Raul C Ribeiro
Gerard P Zambetti
Ramapriya Ganti
Kumar Srivastava
Sheila Shurtleff
Deqing Pei
Luiz Carlos Zeferino
Rozany M Dufloth
Silvia Regina Brandalise
José Andres Yunes
Publication date
01-12-2008
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2008
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-8-357

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