P53 Gene: Mutation and Immunohistochemical Analysis in Patients with Invasive Ductal Carcinoma of Breast
20 Dec 2013-American Journal of Biochemistry and Biotechnology (Science Publications)-Vol. 9, Iss: 4, pp 395-403
TL;DR: It is supported that mutation in p53 gene can be exploited as a prognostic marker for the early diagnosis of breast cancer, although more clinical and epidemiological data is required to establish this claim.
Abstract: The p53 tumor suppressor gene is the most commonly mutated gene in cancer. In breast cancer, the presence of p53 gene alterations has been associated with worse prognosis. This study was attempted to associate p53 gene mutations with its protein expression in North Eastern Indian population. We used single-stranded conformation polymorphism to screen samples for mutations in five conserved regions, exons 4, 5, 6, 7 and 8, of the p53 gene. Mutations were confirmed by direct DNA sequencing. Samples were also analyzed for expression of p53 immunohistochemically. We found two critical mutations in the exon 4. A well known missense mutation at codon 72 (pro to arg) with a frequency of 47% was found which was significantly correlated with the immunohistochemical analysis of p53 protein in such patients. A novel nonsense mutation at codon 107 which leads to stop codon was also found. Although the occurrence of this mutation was very less, we did not find expression of p53 protein immunohistochemicaly. We support that mutation in p53 gene can be exploited as a prognostic marker for the early diagnosis of breast cancer, although more clinical and epidemiological data is required to establish this claim.
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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: It is proposed that the Mdm2-promoted degradation of p53 provides a new mechanism to ensure effective termination of the p53 signal.
Abstract: The p53 tumour-suppressor protein exerts antiproliferative effects, including growth arrest and apoptosis, in response to various types of stress. The activity of p53 is abrogated by mutations that occur frequently in tumours, as well as by several viral and cellular proteins. The Mdm2 oncoprotein is a potent inhibitor of p53. Mdm2 binds the transcriptional activation domain of p53 and blocks its ability to regulate target genes and to exert antiproliferative effects. On the other hand, p53 activates the expression of the mdm2 gene in an autoregulatory feedback loop. The interval between p53 activation and consequent Mdm2 accumulation defines a time window during which p53 exerts its effects. We now report that Mdm2 also promotes the rapid degradation of p53 under conditions in which p53 is otherwise stabilized. This effect of Mdm2 requires binding of p53; moreover, a small domain of p53, encompassing the Mdm2-binding site, confers Mdm2-dependent detstabilization upon heterologous proteins. Raised amounts of Mdm2 strongly repress mutant p53 accumulation in tumour-derived cells. During recovery from DNA damage, maximal Mdm2 induction coincides with rapid p53 loss. We propose that the Mdm2-promoted degradation of p53 provides a new mechanism to ensure effective termination of the p53 signal.
4,311 citations
"P53 Gene: Mutation and Immunohistoc..." refers background in this paper
...In a negative feedback loop, MDM2 is itself induced by the p53 protein (Haupt et al., 1997)....
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TL;DR: It is demonstrated that the majority of women who undergo breast biopsy for benign disease are not at increased risk of cancer, however, patients with a clinically meaningful elevation in cancer risk can be identified on the basis of atypical hyperplasia and a family history of breast cancer.
Abstract: To assess the importance of various risk factors for breast cancer in women with benign proliferative breast lesions, we reevaluated 10,366 consecutive breast biopsies performed in women who had presented at three Nashville hospitals. The median duration of follow-up was 17 years for 3303 women, 1925 of whom had proliferative disease. This sample contained 84.4 per cent of the patients originally selected for follow-up. Women having proliferative disease without atypical hyperplasia had a risk of cancer that was 1.9 times the risk in women with nonproliferative lesions (95 per cent confidence interval, 1.2 to 2.9). The risk in women with atypical hyperplasia (atypia) was 5.3 times that in women with nonproliferative lesions (95 per cent confidence interval, 3.1 to 8.8). A family history of breast cancer had little effect on the risk in women with nonproliferative lesions. However, the risk in women with atypia and a family history of breast cancer was 11 times that in women who had nonproliferative lesions without a family history (95 per cent confidence interval, 5.5 to 24). Calcification elevated the cancer risk in patients with proliferative disease. Although cysts alone did not substantially elevate the risk, women with both cysts and a family history of breast cancer had a risk 2.7 times higher than that for women without either of these risk factors (95 per cent confidence interval, 1.5 to 4.6). This study demonstrates that the majority of women (70 per cent) who undergo breast biopsy for benign disease are not at increased risk of cancer. However, patients with a clinically meaningful elevation in cancer risk can be identified on the basis of atypical hyperplasia and a family history of breast cancer.
1,710 citations
"P53 Gene: Mutation and Immunohistoc..." refers background in this paper
...…epidemiological risk factors for the development of the breast cancer are age at diagnosis, family history, parity, age at the menarche and menopause, diet, socioeconomic status, history of exposure to radiation and use of oral contraceptive pills (Helmrich et al., 2009; Dupont and Page, 1985)....
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TL;DR: The goals of the current study were to fill in the major gaps in knowledge regarding the incidence, presenting characteristics, prognostic factors, and survival rates of male breast carcinoma and to determine how Breast carcinoma differs between men and women.
Abstract: BACKGROUND
Male breast carcinoma is an uncommon disease, and most previous studies have been single-institution series that were limited by extremely small sample sizes. The goals of the current study were to fill in the major gaps in knowledge regarding the incidence, presenting characteristics, prognostic factors, and survival rates of male breast carcinoma and to determine how breast carcinoma differs between men and women.
METHODS
Data from the National Cancer Institute Surveillance, Epidemiology, and End Results 1973–1998 database were used. Age-adjusted incidence rates were calculated. Characteristics of the patients and presenting tumors were compared between men and women. Univariate and multivariate analyses were performed to determine the effect of each variable on overall survival. Survival rates by disease stage were compared for men and women.
RESULTS
Over the years of the study, the incidence of male breast carcinoma increased significantly from 0.86 to 1.08 per 100,000 population (P < 0.001). Men had a higher median age at diagnosis (P < 0.001) and were more likely to have lymph node involvement (P < 0.001), a more advanced stage at diagnosis (P < 0.001), and tumors that were positive for estrogen receptor (ER) (P < 0.001) and progesterone receptor (PR) (P < 0.001). In multivariate analysis, larger tumor size and lymph node involvement were associated with shortened survival. Tumor grade and ER/PR status did not appear to independently influence survival. Relative survival rates by stage of disease for men and women were similar.
CONCLUSIONS
Although it remains a rare disease, the incidence of male breast carcinoma is increasing. Breast carcinoma in men has some epidemiologic and biologic differences from breast carcinoma in women. Cancer 2004. © 2004 American Cancer Society.
669 citations
TL;DR: The RRs for most of these risk factors were modest, but their prevalence as a group was high, leading to estimates that suggest that a substantial proportion of breast cancer cases in the United States are explained by well-established risk factors.
Abstract: Background : Few estimates of the fraction of cases of breast cancer attributable to recognized risk factors have been published. All estimates are based on selected groups, making their generalizability to the U.S. population uncertain. Purpose : Our goal was to estimate the fraction of breast cancer cases in the United States attributable to well-established risk factors (i.e., later age at first birth, nulliparity, higher family income, and first-degree family history of breast cancer), using data from the first National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Follow-up Study (NHEFS), the survey and follow-up of a probability sample of the U.S. population. Methods : From a cohort of 7508 female participants surveyed in the early 1970s, and followed up between 1982 and 1984 and again in 1987, 193 breast cancer cases were accrued for study. We calculated incidence rates, relative risks (RRs), and population attributable risks (PARs) for breast cancer risk factors and extended our results to the U.S. female population by using sample weights from the NHANES I survey. Results : Our PAR estimates suggest that later age at first birth and nulliparity accounted for a large fraction of U.S. breast cancer cases, 29.5% (95% confidence interval [CI] = 5.6%-53.3%); higher income contributed 18.9% (95% CI = -4.3% to 42.1%), and family history of breast cancer accounted for 9.1% (95% CI = 3.0%-15.2%). Taken together, these well-established risk factors accounted for approximately 47% (95% CI = 17%-77%) of breast cancer cases in the NHEFS cohort and about 41% (95% CI = 2%-80%) in the U.S. population. Conclusions : The RRs for most of these risk factors were modest, but their prevalence as a group was high, leading to estimates that suggest that a substantial proportion of breast cancer cases in the United States are explained by well-established risk factors. Implications : Elucidation of the determinants underlying recognized factors and study of other factors that may confer risk or protection are needed in efforts to advance understanding of breast cancer etiology and to aid in devising strategies for prevention.
638 citations
"P53 Gene: Mutation and Immunohistoc..." refers methods in this paper
...Single-Strand Conformation Polymorphism (SSCP) analysis was performed as described by Michaelides et al. (1995)....
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