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Age at diagnosis of cancer as predictor of mutation occurrence in families suspected of HNPCC

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Kurzawski G., Debniak D. T., Debniak T., Kladny K. J., Kladny J., Lubinski L. J., Lubinski J.

Journal of Applied Genetics

2001

vol. 42

issue 3

359-366

Analysis of significance of age at cancer diagnosis as a factor allowing identification of a subgroup of patients with a high frequency of hMSH2 and hMLH1 mutations among families that fulfil suspected HNPCC criteria was performed. DNA from thirty-one unrelated patients affected by colorectal cancer from families matching the above criteria were studied by direct sequencing for occurrence of hMSH2 and hMLH1 gene mutations. Seven unequivocal constitutional mutations were detected: five in the hMLH1 gene and two in the hMSH2 gene. Additionally, one hMLH1 alteration of unknown significance was found. All seven mutations were found in a subgroup of 19 patients with cancer diagnosed before the age of 50 years. In a subgroup of 12 patients with cancer diagnosed at an older age only one case with hMLH1 alteration of unknown significance was detected. Our results indicate that early age at cancer diagnosis seems to be a crucial pedigree factor in discrimination of patients with hMSH2 or hMLH1 mutations among families suspected of HNPCC and matching criteria I of ICG-HNPCC.

Is p53 intronic variant G13964C associated with predisposition to cancer?

80%

Fiszer-Maliszewska L., Kazanowska B., Kusnierczyk P., Manczak M., Niepieklo W., Pochron-Zeman B., Nowakowska B.

Journal of Applied Genetics

2003

vol. 44

issue 4

547-552

Germline mutations of the p53 gene confer a high risk of diverse malignancies. The highest frequency of inherited p53 defects was noted in Li-Fraumeni syndrome (LFS), but almost half of the mutations were found in families with incomplete Li-Fraumeni-like syndrome (LFL), including familial breast cancer cases. Recently, a germline intronic G13964C base change of the p53 was reported as a high-risk mutation associated with familial breast cancer (Lehman et al. 2000). We genotyped Polish cancer patients and healthy control individuals for the G13964C variant. Patients were chosen from cancer families with phenotypes typical for germline mutations of p53 (LFS, LFL), BRCA1 [hereditary breast (ovarian) cancer, HB(O)C] or a complex consistent with both LFL and HB(O)C. Children with leukemia were included in the study as another high risk group (Felix et al. 1992). The G13964C variant was detected in six of 87 (6.9%) cancer patients (including two ALL children), but also in eight of 96 (8.3%) control individuals (p > 0.4). Thus we found no evidence of the variant?s association with a high risk of cancer.

Screening for germline p53 mutations in pediatric and adult patients of high-risk groups in Poland

80%

Fiszer-Maliszewska L., Czernik J., Sawicz-Birkowska K., Perek D., Kozera M., Wojciechowska B., Kazanowska B., Hudziec P., Kilar E.

vol. 48

issue 4

309-315

Germline mutations of the p53 gene lead to cell transformation in various tissues. Such a complex cancer phenotype makes it difficult to recognize the carriers of the defective allele. Several studies undertaken to identify high-risk groups found germline p53 mutations in familial cancer aggregations and in patients with multiple tumors. We screened 189 pediatric and 48 adult patients. The high-risk groups comprised 41 patients with a family history of cancer and 35 with multiple neoplasms. Furthermore, 124 tumors were screened for somatic mutations. p53 exons 2 to 11 were analyzed by polymerase chain reaction and single strand conformation polymorphism (PCR-SSCP) followed by direct sequencing of abnormal DNA fragments. No germline p53 mutations were found and somatic mutations were detected in 5 of 59 sarcomas, globally, in 8 of 124 tumors. In conclusion, in Poland, p53 alterations do not seem very important for the predisposition to malignancy and development of sarcomas.

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2 Journal of Applied Genetics

1 Archivum Immunologiae et Therapiae Experimentalis

1 2003

1 2001

1 2000

2 Fiszer-Maliszewska L.

2 Kazanowska B.

1 Czernik J.

1 Debniak D. T.

1 Debniak T.

1 Hudziec P.

1 Kilar E.

1 Kladny J.

1 Kladny K. J.

1 Kozera M.

1 Kurzawski G.

1 Kusnierczyk P.

1 Lubinski J.

1 Lubinski L. J.

1 Manczak M.

1 Niepieklo W.

1 Nowakowska B.

1 Perek D.

1 Pochron-Zeman B.

1 Sawicz-Birkowska K.

1 Wojciechowska B.

Search results

Age at diagnosis of cancer as predictor of mutation occurrence in families suspected of HNPCC

Is p53 intronic variant G13964C associated with predisposition to cancer?

Screening for germline p53 mutations in pediatric and adult patients of high-risk groups in Poland