The entire TP53 coding sequence, including intron-exon boundaries and UTRs, was analyzed via DHPLC and direct sequencing, and the association of TP53 genotypes with BC risk and with individual lifetime exposures to reproductive factors was investigated with statistical tools.
The most important cause of developing hereditary breast cancer is germline mutations occurring in breast cancer (BCs) susceptibility genes, for example, BRCA1, BRCA2, TP53, CHEK2, PTEN, ATM, and PPM1D.
Patients at risk of hereditary breast cancer unselected for features of LFS carried TP53 pathogenic variants at a frequency comparable to that of other non-BRCA1/2 breast cancer predisposing genes, and ∼threefold more than reported in population controls.
Odds ratio analysis indicated a strong protective role of the RAD51 GG + TP53 ArgArg + XRCC1 RR combined genotype against hereditary breast cancernegative for BRCA1/2 mutations.
However, only about 20% of familial breast cancer is attributed to mutations in BRCA1 and BRCA2, while a further 5-10% are attributed to mutations in other rare susceptibility genes such as TP53, STK11, PTEN, ATM and CHEK2.
However, only about 20% of familial breast cancer cases are attributed to mutations in BRCA1 and BRCA2, while a further 5-10% are attributed to mutations in other rare susceptibility genes such as TP53, STK11, PTEN, ATM and CHEK2.
The most well-established breast molecular markers with prognostic and/or therapeutic value like hormone receptors, HER-2 oncogene, Ki-67, and p53 proteins, and the genes for hereditary breast cancer will be presented.
After excluding BRCA1 and BRCA2 mutations, factors proposed to contribute to familial breast cancer include: chance clustering of apparently sporadic cases, shared lifestyle, monogenic inheritance, i.e., dominant gene mutations associated with a high risk (TP53, PTEN, STK11), dominant gene mutations associated with a relatively low risk (ATM, BRIP1, RLB2), recessive gene mutations associated with horizontal inheritance patterns (sister-sister), and polygenic inheritance where susceptibility to familial breast cancer is thought to be conferred by a large number of low risk alleles.
As low BRD7 expression levels have been linked to p53-wild-type breast tumour cells, we hypothesized an implication of BRD7 germline alterations in the pathogenesis of hereditary breast cancer similar to that of TP53 in Li-Fraumeni syndrome.
In this study we investigated the role of the allelic variants in candidate genes acting in the tumor suppressor, DNA repair and p53 pathways as risk factors for familial breast cancer in 147 patients displaying characteristics of familial disease.
Deleterious mutations of p53 seemed to be responsible for approximately 1% of non-BRCA1/BRCA2 hereditary breast cancer in Chinese population, and our findings suggested that p53 should be included in genetic testing of Chinese non-LFS/non-LFL high-risk breast cancer families.
We performed TP53 mutation analysis and genomewide analysis of loss of heterozygosity and allelic imbalance on DNA from isolated neoplastic epithelial and stromal cells from 43 patients with hereditary breast cancer and 175 patients with sporadic breast cancer.
The present case-control study investigated the association of this SNP (IVS1+309) with the risk and the age of onset of familial breast cancer in patients with unknown p53 mutation status.
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).
Our previous studies have found a high frequency of LOH in the Tp53 region in familial breast cancer suggesting a putative tumor suppressor gene in this region, and the Tp53 gene was excluded as predisposing gene in these families by mutation screening.
In addition, p53 alleles associated with familial breast cancer, previously classified as wild type, showed subtle differences in transactivation capacity towards several REs.
A germ-line mutation in the p53 gene at nucleotide 13964 with a G to C base change (13964GC) was identified in 3 of 42 (7.1%) hereditary breast cancer patients.