Prevalence and Spectrum of Germline Mutations of the p53 Gene among Patients with Sarcoma

Toguchida, Junya; Yamaguchi, Toshikazu; Dayton, Siri H.; Beaughamp, Roberta L.; Herrera, Guillermo E.; Ishizaki, Kanji; Yamamuro, Takao; Meyers, Paul A.; Little, John B.; Sasaki, Masao S.; Weichselbaum, Ralph R.; Yandell, David W.

doi:10.1056/nejm199205143262001

Cited by 280 publications

(123 citation statements)

References 27 publications

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“…Previously reported primer sequences for each exon were used. 25 One microliter of PCR product and 1 ll of size standard TAMRA-350 (Applied Biosystems, Foster City, CA) were denatured in 4 ll of formamide/blue-dextran denaturing buffer at 95°C for 5 min and then loaded onto MDE gels. Gel electrophoresis was carried out on a DNA sequencer (ABI Prism 377, Applied Biosystems) with an external cooling system (Thermo NESLAB, Portsmouth, NH) attached for gels run at 25°C.…”

Section: Mutation Analysismentioning

confidence: 99%

TP53 alterations and patterns of carcinogen exposure in a U.S. population‐based study of bladder cancer

Kelsey

Hirao

et al. 2005

Intl Journal of Cancer

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The molecular pathology of bladder cancer has been the subject of considerable interest, and current efforts are targeted toward elucidating the interrelationships between individual somatic gene loss and both etiologic and prognostic factors. Mutation of the TP53 gene has been associated with more invasive bladder cancer, and evidence suggests that TP53 mutation, independent of stage, may be predictive of outcome in this disease. However, there is no consensus in the literature that bladder carcinogen exposure is associated with inactivation of the TP53 gene. Work to date has been primarily hospital based and, as such, subject to possible bias associated with selection of more advanced cases for study. We examined exposure relationships with both TP53 gene mutation and TP53 protein alterations in a population-based study of 330 bladder cancer cases in New Hampshire. Tobacco smoking was not associated with TP53 alterations. We found a higher prevalence of TP53 inactivation (i.e., mutation and nuclear accumulation) among hair dye users (odd ratio [OR] 5 4.1; 95% confidence interval [CI] 1.2-14.7), and the majority of these mutations were transversions. Men who had ''at risk'' occupations were more likely to have mutated TP53 tumors (OR 5 2.9; 95% CI 1.1-7.6). There also was a relative absence of TP53 mutation (OR 5 0.4; 95% CI 0.0-2.9) and TP53 protein alterations (OR 5 0.6; 95% CI 0.3-1.4) in bladder cancers from individuals with higher arsenic exposure. Our data suggest that there is exposure-specific heterogeneity in inactivation of the TP53 pathway in bladder cancers and that integration of the spectrum of pathway alterations in population-based approaches (capturing the full range of exposures to bladder carcinogens) may provide important insights into bladder tumorigenesis. ' 2005 Wiley-Liss, Inc.

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Section: Mutation Analysismentioning

confidence: 99%

TP53 alterations and patterns of carcinogen exposure in a U.S. population‐based study of bladder cancer

Kelsey

Hirao

et al. 2005

Intl Journal of Cancer

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“…Patients with bone or soft-tissue sarcomas were studied by Toguchida et al (1992), including 181 cases of sporadic disease and 15 patients with an unusual family history of cancer or multiple primary tumours. Three TP53 germline mutations were detected in the former group, but all were subsequently found to have multiple primary tumours or first-degree relatives with sarcomas.…”

Section: Germline Tp53 Mutations In Patients With Tumours Typical Of Lfsmentioning

confidence: 99%

“…Both of these deletions were flanked by short direct repeat sequences. Thirteen other mutations involve short insertion or deletion events (Sameshima et al, 1992;Toguchida et al, 1992;Felix et al, 1993;Birch et al, 1994a;Hamelin et al, 1994;Mazoyer et al, 1994;Stolzenberg et al, 1994;Lubbe et al, 1995;Felix et al, 1996;Varley et al, 1996aVarley et al, , 1997a 1994). Although deletions and insertions are most frequent in exons 2-4 and 9-11 in sporadic tumours (Harris, 1996), in the 114 germline mutations we have reviewed, the situation is not as straightforward.…”

Section: The Spectrum and Type Of Germline Tp53 Mutationsmentioning

confidence: 99%

Li-Fraumeni syndrome – a molecular and clinical review

Varley

Evans²,

Birch³

1997

Br J Cancer

318

180

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“…Over half of all families conforming to the de®nition of classic LFS and approximately one quarter of those which are Li ± Fraumeni-like (LFL, Birch et al, 1994) carry germline mutations to the TP53 gene (Malkin et al, 1990;Birch et al, 1994;Frebourg et al, 1995;Varley et al, 1997). Furthermore, a signi®cant proportion of patients with tumours which are typical of those seen in Li ± Fraumeni syndrome have also been shown to carry TP53 germline mutations at an increased frequency Sameshima et al, 1992;Toguchida et al, 1992;Brugieres et al, 1993;Kyritsis et al, 1994;McIntyre et al, 1994;Wagner et al, 1994;Chen et al, 1995;Diller et al, 1995;Li et al, 1995). TP53 is considered to be a tumour suppressor gene (Hollstein et al, 1991;Levine et al, 1991;Lane, 1992), and as such some tumours from patients with germline TP53 mutations have been analysed for loss of heterozygosity (LOH).…”

Section: Introductionmentioning

confidence: 99%

A detailed study of loss of heterozygosity on chromosome 17 in tumours from Li – Fraumeni patients carrying a mutation to the TP53 gene

et al. 1997

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We have studied a total of 36 tumours from 28 patients with germline mutations to the TP53 gene for loss of heterozygosity at TP53 using techniques of both direct sequencing and restriction fragment length polymorphism analysis. All patients were from families conforming to the de®nition of classical Li ± Fraumeni syndrome (LFS) or were Li ± Fraumeni-like (LFL). The data we have obtained show that loss of the wild-type TP53 gene is observed in under half (44%) of all tumours, and that the pattern of LOH at TP53 may be mutation speci®c. LOH has been observed in premalignant as well as invasive tumours. Two tumours (6%) show loss of the mutant allele and retention of the wild-type. To con®rm that TP53 is indeed the target for LOH events on chromosome 17, we have used additional microsatellite repeats to examine patterns of allelic imbalance along the length of chromosome 17. Data from this analysis indicate that TP53 is the target of loss, but reveal some other interesting patterns of allelic imbalance at other loci on chromosome 17.

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Prevalence and Spectrum of Germline Mutations of the p53 Gene among Patients with Sarcoma

Cited by 280 publications

References 27 publications

TP53 alterations and patterns of carcinogen exposure in a U.S. population‐based study of bladder cancer

TP53 alterations and patterns of carcinogen exposure in a U.S. population‐based study of bladder cancer

Li-Fraumeni syndrome – a molecular and clinical review

A detailed study of loss of heterozygosity on chromosome 17 in tumours from Li – Fraumeni patients carrying a mutation to the TP53 gene

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