Sensitivity and predictive value of criteria for p53germline mutation screening

Chompret, Agnès; Abel, Anne; Stoppa‐Lyonnet, Dominique; Brugières, Laurence; Pagès, Sabine; Feunteun, Jean; Bonaïti‐Pellié, Catherine

doi:10.1136/jmg.38.1.43

Cited by 277 publications

(202 citation statements)

References 38 publications

(13 reference statements)

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“…36 None of these individuals fulfilled classical diagnostic criteria for LFS though all met the Chompret criteria for TP53 testing. 37 Deleterious variants in TP53 were identified in only 1 case of 21 (5%) breast/sarcoma double primaries not fulfilling classical criteria for LFS 38 and not identified in a series of 88 breast cancer cases with a personal or family history of MPMT. 39 De Vivo et al 40 identified 5 individuals harbouring germline PTEN variants (p.Val119Leu x3 and p.Val158Leu x2) from a series of 103 MPMT cases from a cohort of 32 826 nurses.…”

Section: Discussionmentioning

confidence: 98%

A clinical and genetic analysis of multiple primary cancer referrals to genetics services

et al. 2014

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Multiple primary malignant tumours (MPMT) are frequently taken as an indicator of potential inherited cancer susceptibility and occur at appreciable frequency both among unselected cancer patients and, particularly, among referrals to cancer genetics services. However, there is a paucity of information on the clinical genetic evaluation of cohorts of MPMT patients representing a variety of tumour types. We ascertained a referral-based series of MPMT cases and describe the patterns of tumours observed. Service-based molecular genetic testing had demonstrated a pathogenic germline variant in an inherited cancer gene in fewer than one in four unselected referrals. To assess for evidence of thus far unidentified variants in those who tested negative, comparisons were made with those who tested positive. This revealed considerable overlap between the two groups with respect to clinical characteristics indicative of an inherited cancer syndrome. We therefore proceeded to test a subset of unexplained MPMT cases (n ¼ 62) for pathogenic germline variants in TP53 and PTEN but none were detected. Individuals with MPMT may receive negative genetic test results for a number of reasons, which are discussed. Many of these may be addressed by the increasing application of next generation sequencing techniques such as inherited cancer gene panels.

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Section: Discussionmentioning

confidence: 98%

A clinical and genetic analysis of multiple primary cancer referrals to genetics services

et al. 2014

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“…116 For these guidelines, we are adopting a combination of the Eeles and revised Chompret criteria. 117 In two large studies, 29% 118 and 35% 112 of individuals who met the original, slightly more restrictive, Chompret criteria 119 had a TP53 mutation. However, 14% of individuals who met the looser Eeles criteria also had a TP53 mutation.…”

Section: Li-fraumeni Syndrome (Omim 151623)mentioning

confidence: 99%

A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment

Hampel

Bennett

Buchanan

et al. 2015

Genetics in Medicine

449

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Cancer genetic consultation services include the evaluation of patients' personal and family history for concerning features of hereditary cancer predisposition syndromes, development of a differential diagnosis for one or more possible hereditary cancer syndromes, genetic testing if indicated and available, recommendations for management, cancer surveillance and prevention, and information regarding genetic counseling and genetic testing for at-risk relatives. This counseling is informed by the genetic Cancer genetic consultation is an important aspect of the care of individuals at increased risk of a hereditary cancer syndrome. Yet several patient, clinician, and system-level barriers hinder identification of individuals appropriate for cancer genetics referral. Thus, the purpose of this practice guideline is to present a single set of comprehensive personal and family history criteria to facilitate identification and maximize appropriate referral of at-risk individuals for cancer genetic consultation. To develop this guideline, a literature search for hereditary cancer susceptibility syndromes was conducted using PubMed. In addition, GeneReviews and the National Comprehensive Cancer Network guidelines were reviewed when applicable. When conflicting guidelines were identified, the evidence was ranked as follows: position papers from national and professional organizations ranked highest, followed by consortium guidelines, and then peerreviewed publications from single institutions. The criteria for cancer genetic consultation referral are provided in two formats: (i) tables that list the tumor type along with the criteria that, if met, would warrant a referral for a cancer genetic consultation and (ii) an alphabetical list of the syndromes, including a brief summary of each and the rationale for the referral criteria that were selected. Consider referral for a cancer genetic consultation if your patient or any of their firstdegree relatives meet any of these referral criteria.

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“…Indeed, if a p53 mutation segregates in a family in which, by chance, most carriers are males, the classical criteria for diagnosing a Li -Fraumeni syndrome (Li et al, 1988) are most unlikely to be reached and looser criteria (Birch et al, 1994;Varley et al, 1997;Chompret et al, 2001) must be preferred.…”

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confidence: 99%

Sex differences in cancer risk among germline p53 mutation carriers

et al. 2004

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Hwang et al (2003) reported sex difference in cancer risks among p53 germline mutation carriers from a follow-up study of 56 carriers belonging to seven families from a screening of 107 kindreds ascertained through patients with childhood soft tissue sarcoma. We wish to point out that we have reported such sex difference 3 years ago (Chompret et al, 2000). The satisfaction for reading a report confirmatory of our work is mixed by the lack of acknowledgment and discussion of our contribution.Our estimation of cancer risk was based on family data of 295 children treated for a solid tumour at the Institut Gustave-Roussy in Villejuif (France), and screened for p53 germline mutations. This sample was selected among 2691 children treated for a solid tumour, whose family history was investigated between 1991 and 1997 through either of the following criteria: (1) at least one first-or second-degree relative affected by early-onset cancer (45 years or younger); (2) multiple primary cancers in the proband regardless of family history. A total of 17 mutations were found, four of which were de novo mutations, and the remaining 13 were segregating in the families. Blood samples were obtained from first-degree relatives and, when a relative (first-or second-degree or first cousin) was affected by early-onset cancer (i.e. diagnosed before age 46), from all the available family members in that branch of the pedigree. An original method of estimation of cancer risk in carriers (Le Bihan et al, 1995) that takes into account the particular ascertainment design of this family sample was used. Cumulative cancer risks by ages 16, 45 and 85 years were estimated to be respectively 19, 41 and 73% in males, and 12, 84 and 100% in females. There was no difference between males and females in childhood, with an average risk of 15%, but the risks were found to be significantly higher in females than in males in adulthood, and in particular in the 16 -45 age class.We appreciate that cancer risk estimates, obtained from informative and a priori free of any ascertainment bias data, by Hwang et al (2003) are quite similar to ours. The cumulative risks estimated by these authors by ages 20, 30, 40 and 50 years were, respectively, 18, 49, 77 and 93% in female carriers, and 10, 21, 33 and 68% in male carriers. The original finding in this study is that the difference in risk between males and females cannot be explained by the sex-specific cancer, since the difference remained after exclusion of breast, ovary and prostate cancer. Furthermore, they were able to evaluate more accurately the risks at various tumor sites, which was not possible from our data. Only relative risks were estimated, although it would have been interesting to estimate the absolute risks of second cancers, a major issue for germline p53 carriers.The comparison of the results of Hwang et al (2003) to our data allows to draw an interesting conclusion on p53 germline mutations. Although our study used far less stringent criteria than those defining the Li -Fraumeni syndrome (L...

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Sensitivity and predictive value of criteria for p53germline mutation screening

Cited by 277 publications

References 38 publications

A clinical and genetic analysis of multiple primary cancer referrals to genetics services

A clinical and genetic analysis of multiple primary cancer referrals to genetics services

A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment

Sex differences in cancer risk among germline p53 mutation carriers

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