Mutations in p53 do not account for heritable breast cancer: a study in five affected families

Prosser, J.; Elder, P.A.; Condie, Alison; MacFadyen, I; Steel, C. M.; Evans, H. J.

doi:10.1038/bjc.1991.44

Cited by 65 publications

(29 citation statements)

References 31 publications

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“…Some studies have suggested that the tumour-suppressor gene, TP53, is involved in approximately 1% of familial breast cancer cases (Prosser et al, 1991;Sidransky et al, 1992;B0rresen et al, 1992;Lidereau and Soussi, 1992). We studied patients from 109 breast cancer families and found no germline mutation in p53, confirming this low frequency.…”

Section: Discussionsupporting

confidence: 56%

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confidence: 99%

“…Germline mutations have also been found in families with breast and ovarian cancer (Prosser et al, 1992;Jolly et al, 1994). However, germline mutations have not been found to segregate frequently in breast cancer families or patients with early onset or bilateral disease (Prosser et al, 1991;Sidransky et al, 1992;B0rresen et al, 1992;Lidereau and Soussi, 1992).One study, which compared the frequency of somatic TP53 mutations in sporadic breast carcinomas with tumours from patients with a family history, showed that, while sporadic TP53 mutations occurred in 13% of the sporadic tumours, the frequency in the familial cases was 58% (Glebov et al, 1994).We have used constant denaturant gel electrophoresis (CDGE) to screen for germline mutations in exons 5-8 of the TP53 gene in members from 109 breast cancer families. This study also involved searching for mutations in 51 of the tumours from our patients with familial breast cancer.…”

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confidence: 99%

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Screening for TP53 mutations in patients and tumours from 109 Swedish breast cancer families

Zelada-Hedman

Børresen‐Dale²,

Claro³

et al. 1997

Br J Cancer

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Summary To estimate the prevalence of TP53 mutations in familial breast cancer, constant denaturant gel electrophoresis (CDGE) was used to screen exons 5-8 of the TP53 gene for germline mutations. Genomic DNA from 128 breast cancer patients belonging to 109 families with familial cancer were screened. No germline mutations were found in any of the patients. We also studied TP53 mutations in tumour DNA from 51 of the same individuals and found mutations in 14%. This is similar to what has been reported in sporadic breast cancer.Keywords: TP53; p53; mutation analysis; constant denaturant gel electrophoresis; familial breast cancer The p53 protein is a transcription factor and is frequently altered by mutation in most types of cancer. The majority of the mutations are missense mutations (Hollstein et al, 1994).Germline mutations in the TP53 gene were found to segregate in families with the Li-Fraumeni syndrome resulting in a very high risk for early onset breast cancer, sarcoma, leukaemia, brain tumours and other tumours (Malkin, 1994; Wang et al, 1995). It has also been shown that not all families with the classical criteria for Li-Fraumeni segregate a mutation in p53, while some other families with non-classical Li-Fraumeni syndrome do (Birch et al, 1994). Germline mutations have also been found in families with breast and ovarian cancer (Prosser et al, 1992;Jolly et al, 1994). However, germline mutations have not been found to segregate frequently in breast cancer families or patients with early onset or bilateral disease (Prosser et al, 1991;Sidransky et al, 1992;B0rresen et al, 1992;Lidereau and Soussi, 1992).One study, which compared the frequency of somatic TP53 mutations in sporadic breast carcinomas with tumours from patients with a family history, showed that, while sporadic TP53 mutations occurred in 13% of the sporadic tumours, the frequency in the familial cases was 58% (Glebov et al, 1994).We have used constant denaturant gel electrophoresis (CDGE) to screen for germline mutations in exons 5-8 of the TP53 gene in members from 109 breast cancer families. This study also involved searching for mutations in 51 of the tumours from our patients with familial breast cancer. MATERIALS AND METHODS PatientsA total of 128 patients from 109 families with familial cancer, predominantly breast cancer, were identified. The families were selected as described (Lindblom et al, 1992a Correspondence to: A Lindblom number of breast cancer and other cancer diagnoses, the families were categorized as follows: 45 families were defined as breast cancer families and 25 families were defined as cancer families using the following criteria. Breast cancer family -at least three first-or second-degree relatives with breast cancer. Cancer family -the index patient with breast cancer plus at least three first-or second-degree relatives with cancer. The remaining 39 families had a family history of two first-degree relatives with breast cancer. Tumour tissue was available from 51 of these patients.

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Section: Discussionsupporting

confidence: 56%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Screening for TP53 mutations in patients and tumours from 109 Swedish breast cancer families

Zelada-Hedman

Børresen‐Dale²,

Claro³

et al. 1997

Br J Cancer

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“…This frequency is in agreement with the concept that mutations preferentially occur in LFS/LFL-related patients. Zeleda-Hedman et al (1997), Warren et al (1992), Prosser et al (1991) and Patel et al (1995) studied 109, 25, 5 and 4 breast cancer families, respectively, without finding any mutations. Boerresen et al (1992) studied 237 women with breast cancer, of which 30 had at least one first-degree relative with breast cancer, 40 had breast cancer before age 35, and 167 represented unselected breast cancer patients.…”

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confidence: 99%

Germline TP53 alterations in Finnish breast cancer families are rare and occur at conserved mutation-prone sites

Rapakko¹,

Allinen²,

Syrjäkoski

et al. 2001

Br J Cancer

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SummaryWe have screened for germline TP53 mutations in Finnish BRCA1 and BRCA2 mutation-negative families. This study represents the largest survey of the entire protein-encoding portion of TP53, and indicates that mutations are only found at conserved domains in breast cancer families also meeting the criteria for Li-Fraumeni/Li-Fraumeni-like syndrome, explaining only a very small additional fraction of the hereditary breast cancer cases.

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“…Therefore, germ line alterations in gene TP53 probably are not a significant cause of familial breast cancer (17,18).…”

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confidence: 99%

Investigation of single-strand conformational polymorphism of the TP53 gene in women with a family history of breast cancer

Burbano

Medeiros

Mello

et al. 2000

Braz J Med Biol Res

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Breast cancer in families with germ line mutations in the TP53 gene has been described in the medical literature. Mutation screening for susceptibility genes should allow effective prophylactic and preventive measures. Using single-strand conformational polymorphism, we screened for mutations in exons 5, 6, 7 and 8 of gene TP53 in the peripheral blood of 8 young non-affected members (17 to 36 years old) of families with a history of breast cancer. Studies of this type on young patients (mean age, 25 years) are very rare in the literature. The identification of these mutations would contribute to genetic counseling of members of families with predisposition to breast cancer. The results obtained did not show any polymorphism indicating mutation. In our sample, the familial tumorigenesis is probably related to other gene etiologies.

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Mutations in p53 do not account for heritable breast cancer: a study in five affected families

Cited by 65 publications

References 31 publications

Screening for TP53 mutations in patients and tumours from 109 Swedish breast cancer families

Screening for TP53 mutations in patients and tumours from 109 Swedish breast cancer families

Germline TP53 alterations in Finnish breast cancer families are rare and occur at conserved mutation-prone sites

Investigation of single-strand conformational polymorphism of the TP53 gene in women with a family history of breast cancer

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