High frequency of de novo mutations in Li-Fraumeni syndrome

González, Kelly; Buzin, Carolyn H.; Noltner, Katie; Gu, Dongqing; Li, Wenyan; Malkin, David; Sommer, Steve S.

doi:10.1136/jmg.2008.058958

Cited by 152 publications

(106 citation statements)

References 19 publications

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“…Some of the CPC patients with p53 germline mutations do not have any family history of LFS [101,103,112]. Considering that CPC normally occurs early in life, prior to the occurrence of additional LFS-related cancers, it is of high importance to screen all patient with CPC for p53 germline mutations and family history of LFS [113].…”

Section: Cns Tumorsmentioning

confidence: 99%

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Recent developments in brain tumor predisposing syndromes

2015

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Section: Cns Tumorsmentioning

confidence: 99%

“…De novo cases have also been reported. In a report from 2009, 7-20% of the TP53 germline mutations were claimed to be de novo mutations [103].…”

Section: Li-fraumeni (Tp53) Syndrome (Lfs)mentioning

confidence: 99%

Recent developments in brain tumor predisposing syndromes

2015

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“…Clinically, the present study revealed that only one patient with double germline mutations of TP53 D49H and A159D had typical Li-Fraumeni-like syndrome, and the remaining 5 cancer patients had family histories of cancer. Considering the several reports demonstrating that 92-95% of individuals who had germline TP53 pathogenic variants met the revised Chompret criteria for germline TP53 mutation screening (5,18,21), the incidence developing typical clinical features in patients with germline TP53 D49H mutation is lower than expected. According to these information, it is possible to postulate that germline TP53 D49H mutation may have lower pathogenic activities, and that the mutation is likely to be low-penetrant.…”

mentioning

confidence: 99%

Prevalence of low-penetrant germline TP53 D49H mutation in Japanese cancer patients

et al. 2016

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Using whole exome sequencing data obtained from 1,685 Japanese cancer patients, we examined genetic variations of germline TP53 and found 10 types of non-synonymous single nucleotide variants. In the present study, we focused on 6 patients with germline D49H mutation located in the transactivation domain 2 of p53 protein, since the mutation seemed to be prevalent in cancer patients and to be pathogenic. According to the initial survey for family history of the proband with the germline TP53 D49H mutation, one osteosarcoma patient and his pedigree fulfill the criteria for Li-Fraumeni-like syndrome and the 2009 Chompret criteria for germline TP53 mutation screening. Since this patient possesses double germline mutations of TP53 D49H and A159D, further studies are required to evaluate contribution of the D49H mutation in this morbidity. The remaining 5 patients had family histories of cancer, but none fulfills the criteria either for the Li-Fraumeni/Li-Fraumeni-like syndromes or the 2009 Chompret criteria for germline TP53 mutation screening. It is possible to postulate that the germline TP53 D49H mutation is likely to be low-penetrant in some pedigrees. The present study also indicates that the survey for the germline TP53 mutation plays

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“…Most of the current evidence comes from studies in Europe and North America (15). Studies in Brazil have shown that a particular mutant, p.R337H, has incomplete penetrance and may be quite common due to a founder effect (estimated frequency in the general population: 1:300 in certain regions) (16)(17)(18)(19).…”

Section: Discussionmentioning

confidence: 99%