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Prevalence of germline TP53 mutations and history of Li-Fraumeni syndrome in families with childhood adrenocortical tumors, choroid plexus tumors, and rhabdomyosarcoma: A population-based survey.

Magnusson, Susanne LU ; Gisselsson Nord, David LU ; Wiebe, Thomas LU ; Kristoffersson, Ulf LU ; Borg, Åke LU and Olsson, Håkan LU (2012) In Pediatric Blood & Cancer 59(5). p.846-853
Abstract
PURPOSE:

Whether childhood adrenocortical tumors (ACTs), choroid plexus tumors (CPTs), and rhabdomyosarcoma (RMS) are early manifestation of Li-Fraumeni syndrome (LFS) is uncertain. In this study, we evaluated the frequency of germline TP53 mutations and family history in a population-based series of patients.



PATIENTS AND METHODS:

We identified children (≤18 years) diagnosed between 1958 and 2008 with ACT (n = 3) or CPT (n = 7), or children ≤5 years with RMS (n = 29). Registry-based pedigree expansion was performed.



RESULTS:

No patients had a family history of classic LFS but 17 fulfilled Chompret or Eeles criteria. TP53 mutations were found in 1/3 ACT patients and 1/18... (More)
PURPOSE:

Whether childhood adrenocortical tumors (ACTs), choroid plexus tumors (CPTs), and rhabdomyosarcoma (RMS) are early manifestation of Li-Fraumeni syndrome (LFS) is uncertain. In this study, we evaluated the frequency of germline TP53 mutations and family history in a population-based series of patients.



PATIENTS AND METHODS:

We identified children (≤18 years) diagnosed between 1958 and 2008 with ACT (n = 3) or CPT (n = 7), or children ≤5 years with RMS (n = 29). Registry-based pedigree expansion was performed.



RESULTS:

No patients had a family history of classic LFS but 17 fulfilled Chompret or Eeles criteria. TP53 mutations were found in 1/3 ACT patients and 1/18 RMS patients; both were novel mutations. Of five tested CPT patients none had a detectable mutation. No excess of LFS associated tumors was observed, except for breast cancer in families of CPT patients. An overall increased cancer incidence was observed in families of patients with CPT [standardized incidence ratio (SIR) = 2.0; 95% CI: 1.1-3.5] due to excess of breast and female kidney cancer and in families of patients with RMS (SIR = 1.2; 95% CI: 0.9-1.7), due to excess of early-onset melanoma and male stomach cancer.



CONCLUSION:

Relatives of patients with childhood ACTs, CPTs, and RMSs showed no increased risk of LFS associated tumors. However, TP53 mutations could be found in these children irrespective of family history. Absence of LFS associated tumors may suggest the presence of other cancer syndromes. Improved knowledge about relatives' cancer risks could be helpful in counseling family members of children with cancer. Pediatr Blood Cancer © 2012 Wiley Periodicals, Inc. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Pediatric Blood & Cancer
volume
59
issue
5
pages
846 - 853
publisher
John Wiley and Sons Inc.
external identifiers
  • wos:000308656100015
  • pmid:22653678
  • scopus:84866157025
ISSN
1545-5017
DOI
10.1002/pbc.24223
language
English
LU publication?
yes
id
02cf22bc-c555-4682-83a4-4909faa682d0 (old id 2859889)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22653678?dopt=Abstract
date added to LUP
2012-07-04 11:02:03
date last changed
2017-06-18 04:39:15
@article{02cf22bc-c555-4682-83a4-4909faa682d0,
  abstract     = {PURPOSE: <br/><br>
Whether childhood adrenocortical tumors (ACTs), choroid plexus tumors (CPTs), and rhabdomyosarcoma (RMS) are early manifestation of Li-Fraumeni syndrome (LFS) is uncertain. In this study, we evaluated the frequency of germline TP53 mutations and family history in a population-based series of patients. <br/><br>
<br/><br>
PATIENTS AND METHODS: <br/><br>
We identified children (≤18 years) diagnosed between 1958 and 2008 with ACT (n = 3) or CPT (n = 7), or children ≤5 years with RMS (n = 29). Registry-based pedigree expansion was performed. <br/><br>
<br/><br>
RESULTS: <br/><br>
No patients had a family history of classic LFS but 17 fulfilled Chompret or Eeles criteria. TP53 mutations were found in 1/3 ACT patients and 1/18 RMS patients; both were novel mutations. Of five tested CPT patients none had a detectable mutation. No excess of LFS associated tumors was observed, except for breast cancer in families of CPT patients. An overall increased cancer incidence was observed in families of patients with CPT [standardized incidence ratio (SIR) = 2.0; 95% CI: 1.1-3.5] due to excess of breast and female kidney cancer and in families of patients with RMS (SIR = 1.2; 95% CI: 0.9-1.7), due to excess of early-onset melanoma and male stomach cancer. <br/><br>
<br/><br>
CONCLUSION: <br/><br>
Relatives of patients with childhood ACTs, CPTs, and RMSs showed no increased risk of LFS associated tumors. However, TP53 mutations could be found in these children irrespective of family history. Absence of LFS associated tumors may suggest the presence of other cancer syndromes. Improved knowledge about relatives' cancer risks could be helpful in counseling family members of children with cancer. Pediatr Blood Cancer © 2012 Wiley Periodicals, Inc.},
  author       = {Magnusson, Susanne and Gisselsson Nord, David and Wiebe, Thomas and Kristoffersson, Ulf and Borg, Åke and Olsson, Håkan},
  issn         = {1545-5017},
  language     = {eng},
  number       = {5},
  pages        = {846--853},
  publisher    = {John Wiley and Sons Inc.},
  series       = {Pediatric Blood & Cancer},
  title        = {Prevalence of germline TP53 mutations and history of Li-Fraumeni syndrome in families with childhood adrenocortical tumors, choroid plexus tumors, and rhabdomyosarcoma: A population-based survey.},
  url          = {http://dx.doi.org/10.1002/pbc.24223},
  volume       = {59},
  year         = {2012},
}