Transmission of a TP53 germline mutation from unaffected male carrier associated with pediatric glioblastoma in his child and gestational choriocarcinoma in his female partner
- Jennifer A. Cotter1,
- Linda Szymanski1,
- Catherine Karimov2,
- Lara Boghossian2,
- Ashley Margol3,
- Girish Dhall3,
- Benita Tamrazi4,
- G. Isaac Varaprasathan5,
- David M. Parham1,
- Alexander R. Judkins1 and
- Jaclyn A. Biegel1
- 1Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Keck School of Medicine of University of Southern California, Los Angeles, California 90027, USA;
- 2Department of Medical Genetics, Children's Hospital Los Angeles, Keck School of Medicine of University of Southern California, Los Angeles, California 90027, USA;
- 3Department of Pediatrics, Children's Hospital Los Angeles, Keck School of Medicine of University of Southern California, Los Angeles, California 90027, USA;
- 4Department of Radiology, Children's Hospital Los Angeles, Keck School of Medicine of University of Southern California, Los Angeles, California 90027, USA;
- 5Antelope Valley Hospital Medical Center, Lancaster, California 93534, USA
- Corresponding author: jcotter{at}chla.usc.edu
Abstract
Li–Fraumeni syndrome (LFS) is an autosomal dominant cancer predisposition syndrome caused by germline alterations in the tumor suppressor gene TP53. LFS is associated with numerous malignancies including astrocytoma. Sanger sequencing and chromosomal microarray studies of blood and tumor tissue from a 4-yr-old boy with glioblastoma demonstrated a germline TP53 mutation with loss of heterozygosity for the short arm of Chromosome 17 as the second inactivating event in the tumor. There was no family history of LFS, but the child's mother had recently died from metastatic choriocarcinoma after antecedent normal term delivery of a then 6-mo-old daughter. The choriocarcinoma contained the same TP53 mutation detected in the proband and the 6-mo-old daughter was confirmed to be a carrier. Unexpectedly, the germline TP53 mutation was found to be inherited from the unaffected father. We report here the second genetically confirmed case of TP53-mutated choriocarcinoma in the partner of an LFS patient. Based on this case and recent literature, female partners of LFS patients may have increased risk of choriocarcinoma due to transmission of germline TP53 mutation from male carriers. Although the Toronto protocol has established an effective approach to detect tumors and improve survival in children and adults with LFS, there is a need to expand the current criteria to include surveillance of female partners of LFS patients for choriocarcinoma and other gestational trophoblastic disease. Recognition of this unique mode of transmission of TP53 mutations should be considered in genetic counseling for cancer risk assessment and family planning.
- Received December 13, 2017.
- Accepted February 8, 2018.
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