The prevalence of germ-line TP53 mutations in women diagnosed with breast cancer before age 30

Ginsburg, Ophira; Akbari, Mohammad Reza; Aziz, Zeba; Young, Robert H.; Lynch, Henry T.; Ghadirian, Parviz; Robidoux, André; Londoño, Julián Esteban Zamarra; Vásquez, Gonzalo; Gomes, Magda; Costa, Mauricio Magalhaes; Dimitrakakis, Constantine; Gutiérrez, Gustavo; Pilarski, Robert; Royer, Robert E.; Narod, Steven A.

doi:10.1007/s10689-009-9287-z

Cited by 35 publications

(27 citation statements)

References 28 publications

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“…Breast cancer at young age was not included in the 2009 revised Chompret criteria because they concluded that the mutation detection rate for patients with early onset breast cancer without a family history of cancer or multiple primary tumours was <5% 7. Ginsburg et al did not find any TP53 mutations in 95 sporadic breast cancer cases under 30 years of age 28. Testing adrenal cortical carcinoma patients for germline TP53 mutations revealed a 50–97% chance of finding a mutation 29–32.…”

Section: Discussionmentioning

confidence: 99%

TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes

Ruijs

Verhoef

Rookus

et al. 2010

Journal of Medical Genetics

258

168

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General rightsIt is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. germline mutations may also occur in less obvious phenotypes. As a result, different criteria are in use to decide which patients qualify for TP53 mutation analysis, including the LFS, LieFraumeni-like (LFL) and Chompret criteria. We investigated which criteria for TP53 mutation analysis resulted in the highest mutation detection rate and sensitivity in Dutch families. We describe the tumour spectrum in TP53-positive families and calculated tumour type specific relative risks. Method A total of 180 Dutch families referred for TP53 mutation analysis were evaluated. Tumour phenotypes were verified by pathology reports or clinical records.Results A TP53 germline mutation was identified in 24 families. When the Chompret criteria were used 22/24 mutations were detected (sensitivity 92%, mutation detection rate 21%). In LFS and LFL families 18/24 mutations were found (sensitivity 75%). The two mutations detected outside the 'Chompret group' were found in a child with rhabdomyosarcoma and a young woman with breast cancer. In the mutation carriers, in addition to the classical LFS tumour types, colon and pancreatic cancer were also found significantly more often than in the general population. Conclusion We suggest TP53 mutation testing for all families fulfilling the Chompret criteria. In addition, TP53 mutation testing can be considered in the event of childhood sarcoma and breast cancer before 30 years. In addition to the risk for established LFS tumour types, TP53-positive individuals may also have an elevated risk for pancreatic and colon cancer.

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Section: Discussionmentioning

confidence: 99%

TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes

Ruijs

Verhoef

Rookus

et al. 2010

Journal of Medical Genetics

258

168

View full text Add to dashboard Cite

show abstract

“…Mean age at first cancer diagnosis among females heterozygous for a germline TP53 mutation in one prospective cohort was 29 years [9]. The reported frequency of germline TP53 mutations in population-based series of women diagnosed with unselected invasive breast cancer before age 30 years ranges from <1% to 4% [5, 12]. …”

Section: Introductionmentioning

confidence: 99%

Prevalence of germline TP53 mutations in HER2+ breast cancer patients

Rath

Masciari

Gelman

et al. 2013

Breast Cancer Res Treat

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Background Breast cancer is the most frequent tumor in Li-Fraumeni syndrome (LFS), a rare inherited cancer syndrome associated with germline mutations in the TP53 gene. Recent data show that breast cancer in germline TP53 mutation carriers is commonly HER2-positive (63–83%). We assessed the prevalence of germline TP53 mutations in a cohort of women with HER2+ breast cancer diagnosed age ≤ 50 years. Material & Methods We identified blood specimens from 213 women with primary invasive HER2+ breast cancer age ≤ 50 years from a single center. EGAN sequencing and MLPA techniques were used to screen for germline TP53 mutations. Results Among 213 women with HER2+ breast cancer age ≤ 50 years, 3 (ages at diagnosis 23, 32, 44 years) were found to carry a TP53 mutation (1.4%, 95%CI 0.3%–4.1%). ER/PR status was not uniform. Two TP53-carriers met Chompret criteria for LFS; none met classic LFS criteria. Conclusion Although two-thirds of breast cancers in women with TP53 mutations are HER2+, we observed a low prevalence of germline TP53 mutations among unselected young women with HER2+ breast cancer. Given the potential clinical impact, consideration of germline TP53 testing should be given to young women with HER2+ breast cancer, especially if family cancer history is notable.

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“…Prevalence of TP53 mutations ranging from less than 1 to 5% has been reported in studies conducted in Caucasian populations [15][16][17][18][19][20][21][22][23][24]. Few data exist on the contribution of TP53 to early-onset breast cancer in Non-Caucasian populations.…”

Section: Introductionmentioning

confidence: 99%

Prevalence of TP53 germ line mutations in young Pakistani breast cancer patients

et al. 2012

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Women from Pakistan and India are more often diagnosed with early-onset breast cancer than Caucasian women. Given that only 12% of Pakistani women diagnosed with breast cancer at or before 30 years of age have previously been shown to harbor germ line mutations in the breast cancer susceptibility genes BRCA1 and BRCA2, the genetic causes of the majority of early-onset cases are unexplained. Since germ line mutations in the tumor suppressor gene TP53 predispose women to early-onset breast cancer, we assessed the prevalence of TP53 mutations in 105 early-onset breast cancer patients from Pakistan, who had previously been found to be negative for BRCA1 and BRCA2 germ line mutations. The patient group included 67 women diagnosed with early-onset breast cancer at or before age 30 with no family history of breast or ovarian cancer (EO30NFH group) and 38 women diagnosed with breast cancer at or before age 40 with one or more first- or second-degree relatives with breast or ovarian cancer (EO40FH group). Mutation analysis of the complete TP53 coding region was performed using denaturing high-performance liquid chromatography analysis, followed by DNA sequencing of variant fragments. One deleterious mutation, c.499-500delCA in exon 5, was identified in the 105 breast cancer patients (1%). This mutation is novel in the germ line and has not been described in other populations. It was detected in a 28-year-old patient with no family history of breast or ovarian cancer. This mutation is rare as it was not detected in additional 157 recently recruited non-BRCA1 and non-BRCA2-associated early-onset breast cancer patients. Our findings show that TP53 mutations may account for a minimal portion of early-onset breast cancer in Pakistan.

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The prevalence of germ-line TP53 mutations in women diagnosed with breast cancer before age 30

Cited by 35 publications

References 28 publications

TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes

TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes

Prevalence of germline TP53 mutations in HER2+ breast cancer patients

Prevalence of TP53 germ line mutations in young Pakistani breast cancer patients

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