Absence of P53 Gene Mutations in Exons 5 - 7 Among Breast Cancer Patients of Bengalee Hindu Caste Females, West Bengal, India
01 Jan 2012-Asian Pacific Journal of Cancer Prevention (Asian Pac J Cancer Prev)-Vol. 13, Iss: 9, pp 4477-4479
TL;DR: It is concluded that mutations in exons 5-7 of p53 gene are rare causes of breast cancer among Bengalee Hindu caste females, and therefore of little help for genetic counseling and diagnostic purposes.
Abstract: Background: The high incidence and relatively good prognosis of breast cancer has made it the most prevalent cancer in the world today. A large number of distinct mutations and polymorphisms in the p53 gene have been reported worldwide, but there is no report regarding the role of this inherited susceptibility gene in breast cancer risk among the Bengalee Hindu Caste females of West Bengal, India. Aim of the Study: We investigated the distribution and the nature of p53 gene mutations and polymorphisms in exons 5-7 in a cohort of 110 Bengalee Hindu breast cancer patients and 127 age, sex and caste matched controls by direct sequencing. Results: We did not observe any mutations and polymorphisms in our studied individuals. Conclusion: We therefore conclude that mutations in exons 5-7 of p53 gene are rare causes of breast cancer among Bengalee Hindu caste females, and therefore of little help for genetic counseling and diagnostic purposes.
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TL;DR: The intron 3 16 bp duplication polymorphism of p53 could not be assessed as a marker of risk factor for predisposition to breast cancer in Azeri population, however, a high frequency of A2 allele (22.1%) in the population suggested that intron 2 15 bp duplicated polymorphism may be a valuable marker for study in other cancers with well designed large groups.
Abstract: Background: p53 gene is a well-known tumor suppressor gene that has several polymorphisms in both its exons and introns. It has been suggested that intron 3 16 bp duplication polymorphism may affect the gene function resulting in reduction or suppression of p53 anti tumor activity. In most case control studies a duplicated allele has been noticeably more frequent in cases rather than controls but there are also conflicting results. The aim of this study was to assess the association of intron 3 16 bp duplication polymorphism of p53 with breast cancer risk among Iranian-Azeri population. We also analyzed the clinicopathological information of patients as an epidemiological description of breast cancer in the north-west of Iran. Materials and Methods: This casecontrol study was performed on 221 breast cancer patients and 170 controls. Genomic DNA was extracted from peripheral blood samples and tumor tissues. p53 PIN3 genotype was determined using electrophoresis of PCR products on 8% non-denaturing polyacrylamide gels and silver staining. Results: In the control and case groups, respectively, 62.9% and 61.1% had no 16 bp insertion (A1A1 genotype), 7.1% and 7.7% had insertion in both p53 alleles (A2A2) and 30% and 31.2% were heterozygous (A1A2). There was no significant difference between genotype frequencies as well as allelic frequencies in two case and control groups. Conclusions: According to the result of the present study, the intron 3 16 bp duplication polymorphism of p53 could not be assessed as a marker of risk factor for predisposition to breast cancer in Azeri population. However, a high frequency of A2 allele (22.1%) in our population suggested that intron 3 16 bp duplication polymorphism may be a valuable marker for study in other cancers with well designed large groups.
8 citations
TL;DR: According to the preliminary genetic analysis, PIN3 Ins16pb polymorphism could not be assessed as a marker of risk factor for predisposition to breast cancer in Moroccan population, however, a high frequency of A2 allele in the population suggested that PIN3ins16bp polymorphism may be a valuable marker for study in other cancers with larger groups.
Abstract: TP53 is a tumor suppressor gene involved in cell cycle progression control, DNA damage repair, genomic stability, and apoptosis. Some polymorphisms in this gene have been associated with the development of a number of cancers including breast carcinoma. PIN3 Ins16bp polymorphism has been widely studied in different populations for an association with breast cancer risk. In most case-control studies, a duplicated allele has been more frequent in cases rather than controls but there are also inconsistent results. The present study aimed to assess the association of PIN3 Ins16bp polymorphism of p53 with breast cancer risk in Moroccan population. This case-control study was performed on 105 female patients with confirmed breast cancer and 114 healthy controls. The genotype frequency was 69.5 % (A1A1), 26.7 % (A1A2), and 3.8 % (A2A2) in patients and 68.4 % (A1A1), 24.6 % (A1A2), and 7 % (A2A2) in controls. No statistically significant association was observed between PIN3 Ins16bp polymorphism and breast cancer risk with odds ratio of 1.07 (confidence interval (CI) = 0.58–1.97, p = 0.83) for the heterozygous A1A2 and 0.53 (CI = 0.15–1.85, p = 0.32) for mutated homozygous A2A2.According to our preliminary genetic analysis, PIN3 Ins16pb polymorphism could not be assessed as a marker of risk factor for predisposition to breast cancer in Moroccan population. However, a high frequency of A2 allele (19.3 %) in our population suggested that PIN3 Ins16pb polymorphism may be a valuable marker for study in other cancers with larger groups.
4 citations
Cites background from "Absence of P53 Gene Mutations in Ex..."
...Three p53well studied functional polymorphisms include Arg/Pro polymorphism in exon 4, 16bp duplication in intron 3 (PIN3), and intron 6 G13964C alteration [12], although two studies in India showed no link between polymorphisms and breast cancer [13, 14]....
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References
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Book•
15 Jan 2001
TL;DR: Molecular Cloning has served as the foundation of technical expertise in labs worldwide for 30 years as mentioned in this paper and has been so popular, or so influential, that no other manual has been more widely used and influential.
Abstract: Molecular Cloning has served as the foundation of technical expertise in labs worldwide for 30 years. No other manual has been so popular, or so influential. Molecular Cloning, Fourth Edition, by the celebrated founding author Joe Sambrook and new co-author, the distinguished HHMI investigator Michael Green, preserves the highly praised detail and clarity of previous editions and includes specific chapters and protocols commissioned for the book from expert practitioners at Yale, U Mass, Rockefeller University, Texas Tech, Cold Spring Harbor Laboratory, Washington University, and other leading institutions. The theoretical and historical underpinnings of techniques are prominent features of the presentation throughout, information that does much to help trouble-shoot experimental problems. For the fourth edition of this classic work, the content has been entirely recast to include nucleic-acid based methods selected as the most widely used and valuable in molecular and cellular biology laboratories. Core chapters from the third edition have been revised to feature current strategies and approaches to the preparation and cloning of nucleic acids, gene transfer, and expression analysis. They are augmented by 12 new chapters which show how DNA, RNA, and proteins should be prepared, evaluated, and manipulated, and how data generation and analysis can be handled. The new content includes methods for studying interactions between cellular components, such as microarrays, next-generation sequencing technologies, RNA interference, and epigenetic analysis using DNA methylation techniques and chromatin immunoprecipitation. To make sense of the wealth of data produced by these techniques, a bioinformatics chapter describes the use of analytical tools for comparing sequences of genes and proteins and identifying common expression patterns among sets of genes. Building on thirty years of trust, reliability, and authority, the fourth edition of Mol
215,169 citations
TL;DR: The p53 mutational spectrum differs among cancers of the colon, lung, esophagus, breast, liver, brain, reticuloendothelial tissues, and hemopoietic tissues as mentioned in this paper.
Abstract: Mutations in the evolutionarily conserved codons of the p53 tumor suppressor gene are common in diverse types of human cancer. The p53 mutational spectrum differs among cancers of the colon, lung, esophagus, breast, liver, brain, reticuloendothelial tissues, and hemopoietic tissues. Analysis of these mutations can provide clues to the etiology of these diverse tumors and to the function of specific regions of p53. Transitions predominate in colon, brain, and lymphoid malignancies, whereas G:C to T:A transversions are the most frequent substitutions observed in cancers of the lung and liver. Mutations at A:T base pairs are seen more frequently in esophageal carcinomas than in other solid tumors. Most transitions in colorectal carcinomas, brain tumors, leukemias, and lymphomas are at CpG dinucleotide mutational hot spots. G to T transversions in lung, breast, and esophageal carcinomas are dispersed among numerous codons. In liver tumors in persons from geographic areas in which both aflatoxin B1 and hepatitis B virus are cancer risk factors, most mutations are at one nucleotide pair of codon 249. These differences may reflect the etiological contributions of both exogenous and endogenous factors to human carcinogenesis.
8,063 citations
TL;DR: The cell cycle is composed of a series of steps which can be negatively or postively regulated by various factors, chief among the negative regulators is the p53 protein, which can lead to cancer.
Abstract: The cell cycle is composed of a series of steps which can be negatively or positively regulated by various factors. Chief among the negative regulators is the p53 protein. Alteration or inactivation of p53 by mutation, or by its interactions with oncogene products of DNA tumour viruses, can lead to cancer. These mutations seem to be the most common genetic change in human cancers.
3,665 citations
"Absence of P53 Gene Mutations in Ex..." refers background in this paper
...This suggests an etiological role of exogenous chemical carcinogenesis in sporadic breast carcinoma (Levine et al., 1991)....
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Journal Article•
TL;DR: Mutation within a highly conserved region of the p53 gene leading to overexpression of the protein product can occur in the earliest recognized phase of breast cancer and this alteration is maintained during progression from intraductal to infiltrating carcinoma.
Abstract: Overexpression of the nuclear phosphoprotein p53 is one of the most common abnormalities in primary human cancer and appears to be due to point mutation within a highly conserved region of the p53 gene which then encodes for a mutant, more stable protein. In this study different stages of breast cancer progression were examined, from in situ to metastatic disease, to determine at what stage mutational activation occurs and whether it is maintained during tumor progression. Two (13%) of 15 pure intraductal tumors expressed high levels of p53 in all malignant epithelial cells. Sequencing of p53 mRNA from one of these tumors demonstrated a nucleotide substitution altering the amino acid composition of the protein. Six (17%) of 35 specimens which contained both in situ and invasive disease expressed high levels of p53. All malignant epithelial cells in these 6 cases stained positively and in no specimen did one component express different levels of the protein than the other growth phase. Sequence analysis of a tissue with significant amounts of both in situ and invasive disease revealed only a single point mutation, without evidence of wild-type nucleotide at the site of substitution, suggesting that p53 mRNA from each component of the tumor contained the same nucleotide substitution. Eleven (50%) of 22 pairs of primary tumors and their lymph node metastases expressed elevated levels of p53, and in each case, expression levels were identical in the primary and secondary sties. Identical mutations were found in the p53 mRNA from two paired primary and metastatic sites. Therefore, mutation within a highly conserved region of the p53 gene leading to overexpression of the protein product can occur in the earliest recognized phase of breast cancer and this alteration is maintained during progression from intraductal to infiltrating carcinoma. Mutations are also conserved during the process of metastatic spread.
243 citations
Journal Article•
TL;DR: Altered changes to p53, whether loss of one allele or mutation, are by far the most common changes so far detected in primary human breast tumours.
Abstract: DNAs from ninety seven primary breast carcinoma biopsies have been examined for loss of sequences on 17p13. In addition, immunohistochemical analysis has been carried out on the majority of these cases to determine whether p53 gene expression can be detected. Detection of p53 expression is taken to indicate mutation of p53 leading to stabilisation of the protein and thus detectable levels of p53 in the cell. In 86% of breast carcinoma samples where both allele loss and expression data were available, loss of sequences on 17p13 and/or expression of p53 was detected. Alterations to p53, whether loss of one allele or mutation, are therefore by far the most common changes so far detected in primary human breast tumours. In three cases where expression of p53 could be detected by immunohistochemistry, the precise mutation to p53 was identified. All three mutations fall within the regions which are highly conserved in p53, encoded by exons 5 to 8. Two are single base changes leading to misense mutations, and the third is a single base-pair deletion. The expression of the latter gene would result in production of a truncated protein which should lack normal biological activities.
202 citations