Adrenocortical tumors associated with the TP53 p. R337H germline mutation can be identified during child-care consultations / Tumores adrenocorticais associados à mutação germinativa TP53 p. R337H podem ser identificados durante as consultas de puericultura

Abstract Objective: To evaluate the clinical features associated with adrenocortical hormone overexpression and familial cancer profiling as potential markers for early detection of adrenocortical tumors in children from South and Southeast Brazil. Methods: The clinical manifestations and anthropometric measurements of 103 children diagnosed with adrenocortical tumors were analyzed. Results: Between 1982 and 2011, 69 girls and 34 boys diagnosed with adrenocortical tumors were followed-up for a median time of 9.0 years (0-34 years). Signs of androgen overproduction alone (n = 75) or associated with cortisol (n = 18) were present in 90.3%. TP53 p.R337H mutation was found in 90.5% of patients. Stages I, II, III, and IV were observed in 45.6%, 27.2%, 19.4%, and 7.8% of patients, respectively. At diagnosis, there were no significant differences in height (p = 0.92) and weight (p = 0.22) among children with adrenocortical tumors, but children with virilization alone had significantly higher height-for-age Z-scores (0.92 ± 1.4) than children with hypercortisolism alone or combined (−0.32 ± 1,8; p = 0.03). The five-year overall survival was 76.7% (SD ± 4.2). Patients with advanced-stage disease had a significantly worse prognosis than those with limited disease (p < 0.001). During follow-up, ten of 55 p.R337H carrier parents developed cancer, whereas none of the 55 non-carriers did. Conclusions: Signs of adrenocortical hormone overproduction appear early, even in cases with early-stage. These signs can be identified at the physical examination and anthropometric measurements. In southern Brazil, pediatric adrenocortical tumor is a sentinel cancer for detecting families with germline p.R337H mutation in TP53 gene.

Resumo Objetivo: Avaliar as manifestações clínicas da hiperexpressão de hormônios do córtex da adrenal e câncer familiar como marcadores para a detecção precoce de tumores adrenocorticais em crianças do Sul e Sudeste do Brasil. Pacientes e métodos: Foram analisadas as manifestações clínicas e antropométricas de 103 crianças diagnosticadas com tumores adrenocorticais. Resultados: Entre 1982 e 2011, 69 meninas e 34 meninos diagnosticados com tumores adrenocorticais foram acompanhados por um tempo mediano de nove anos (0-34). Ao diagnóstico, sinais de virilização isolada (n = 75) ou associada ao cortisol (n = 18) estavam presentes em 90,3% dos pacientes; a mutação do gene TP53 p.R337H foi identificada em 90,5% dos pacientes. Os pacientes foram classificados em estádio I (45,6%), II (27,2%), III (19,4%) e IV (7,8%). Ao diagnóstico, não houve diferença significativa para as medidas de altura (p = 0,92) e de peso (p = 0,22) entre as crianças com tumores adrenocorticais, mas crianças com virilização tiveram escore-Z mais elevado para a idade (0,92 ± 1,4) do que aquelas com hipercortisolismo isolado ou combinado (−0,32 ± 1,8; p = 0,03). A sobrevida global de cinco anos foi de 76,7% (DP ± 4,2). Pacientes com estádios avançados tiveram pior prognóstico (p < 0,001). Durante o seguimento, 10 dos 55 genitores portadores da p.R337H desenvolveram câncer, enquanto que nenhum caso ocorreu entre os 55 não portadores. Conclusões: Os sinais de hiperprodução de hormônios adrenocorticais aparecem precocemente no desenvolvimento do tumor e podem ser identificados pelo exame físico e pelas medidas antropométricas na consulta pediátrica de rotina. O tumor adrenocortical pediátrico é sentinela para a detecção de câncer em famílias que segregam a mutação germinativa p.R337H do gene TP53.

Exome sequence analysis of Kaposiform hemangioendothelioma: identification of putative driver mutations

Abstract BACKGROUND: Kaposiform hemangioendothelioma is a rare, intermediate, malignant tumor. The tumor's etiology remains unknown and there are no specific treatments. OBJECTIVE: In this study, we performed exome sequencing using DNA from a Kaposiform hemangioendothelioma patient, and found putative candidates for the responsible mutations. METHOD: The genomic DNA for exome sequencing was obtained from the tumor tissue and matched normal tissue from the same individual. Exome sequencing was performed on HiSeq2000 sequencer platform. RESULTS: Among oncogenes, germline missense single nucleotide variants were observed in the TP53 and APC genes in both the tumor and normal tissue. As tumor-specific somatic mutations, we identified 81 candidate genes, including 4 nonsense changes, 68 missense changes and 9 insertions/deletions. The mutations in ITGB2, IL-32 and DIDO1 were included in them. CONCLUSION: This is a pilot study, and future analysis with more patients is needed to clarify: the detailed pathogenesis of this tumor, the novel diagnostic methods by detecting specific mutations, and the new therapeutic strategies targeting the mutation.

Analysis of p53, K-ras gene mutation & Helicobacter pylori infection in patients with gastric cancer & peptic ulcer disease at a tertiary care hospital in north India.

Background & objectives: Mutations in the oncogene and tumour suppressor genes play an important role in carcinogenesis. We investigated the association of p53 and K-ras gene mutation and Helicobacter pylori infection in patients with gastric cancer (GC) and peptic ulcer disease (PUD) attending a tertiary care hospital in north India. Methods: In total, 348 adult patients [62 GC, 45 PUD and 241 non-ulcer dyspepsia (NUD)] who underwent an upper gastrointestinal endoscopy were enrolled. H. pylori infection was diagnosed by rapid urease test, culture, histopathology and PCR. Mutation in the exon 5-8 of p53 gene was analyzed by PCR-single stranded conformational polymorphism (SSCP) and confirmed by sequence analysis. K-ras gene codon 12 mutation was analyzed by PCR-based restriction fragment length polymorphism. Results: Overall p53 gene mutation was found in 4.6 per cent of the study population, and its distribution in GC, PUD and NUD was 21, 4.4 and 0.4 per cent, respectively. p53 gene mutation was significantly higher in patients with GC than PUD (P<0.05) and NUD (P<0.001). No difference in p53 gene mutation was observed between H. pylori infected and non-infected individuals. K-ras gene mutation was absent in all the patients. Interpretation & conclusions: Our results show that p53 gene mutation may be associated with gastric carcinogenesis independent to H. pylori infection and absence of K-ras gene mutation questions its role in the pathogenesis of GC and PUD in Indian patients.

[ prevalence of P53 mutations in laryngeal cancer in Kerman]

Laryngeal cancer is the second common cancer of respiratory tract, following the lung cancer. Carcinogenesis is a complex multistage process; molecular genetics has provided the evidence that activation of proto-oncogene and loss or inactivation of tumor suppressor genes [TSG] are involved in a large number of malignancies. One of the earliest significant tumor suppressor genes identified in head and neck squamous cell carcinoma [HNSCC] was P53 have a role in growth suppression activities. Thus, when P53 is deleted or silenced, the cell develops a selective growth advantage and becomes a cancer. Mutations in P53 are correlated with poorer survival and response to treatment. The aim of this study was to survey the prevalence of P53 gene mutation in patients with laryngeal cancer and to select an appropriate method of treatment. The samples were 52 patients with laryngeal cancer diagnosis have been treated by surgery. Investigation of TP53 mutation where performed by multiple ligation probe amplification [MLPA] technique which analyze the full length of gene from exon 1 to 12. The TP53 mutation was discovered in 80.8 percent of samples. By contrast between two main forms of mutation [i.e. deletions and duplications], we found that the deletions mostly occurred within exons 1, 3, 6, 9 and 12 by 59.6 percent and duplications observed in exons 1, 2, 7, 8 and 11 by 21.2 percent. Considering our results and reminding this fact that nowadays the definitive diagnosis of laryngeal cancer is made using biopsy and pathology techniques, we suggest that all biopsy specimens should be tested and those confirmed positive for TP53 mutations need some further decisions by physicians

Immunohistochemical expression of ki-67 and p53 in colorectal adenomas: a clinicopathological study

To evaluate the significance of P53 and Ki-67 expression as immunohistochemical markers in early detection of premalignant changes in different types of colorectal adenomas. Also, to correlate immunohistochemical expression of the two markers with different clinicopathological parameters including; age, and sex of the patient, type, site, size and grade of dysplasia of colorectal adenomas. Forty-seven polypectomy specimens of colorectal adenomas were retrieved from the archival materials of the Gastrointestinal and Hepatic Diseases Teaching Hospital in Baghdad from 2009-2010. Four ?m section specimens were stained by immunohistochemical technique with Ki-67 and P53 tumor markers. P-values<0.05 were considered statistically significant. Immunohistochemical expressions of Ki-67 and P53 had a significant correlation with the size and grade of dysplasia in colorectal adenomas. However, there was no significant correlation among the immunohistochemical expression of Ki-67 and P53 with the age and gender of the patient, and the type and site of colorectal adenomas. There was no significant correlation between Ki-67 and P53 expressions in colorectal adenomas. Villous adenomas of colorectum showed a significant correlation with the grade of dysplasia, while there was no significant correlation between size and site of colorectal adenoma with the grade of dysplasia. High grade dysplasia with significant positive immunohistochemical markers of Ki-67 and P53 could be valuable parameters for selecting from the total colorectal adenoma population, those most deserving of close surveillance in followup cancer prevention programs. It is closely linked with increasing age particularly in patients with a large size adenoma of villous component in their histology

Prognostic significance of ER, PR, Ki67, c-erbB-2, and p53 in endometrial carcinoma.

OBJECTIVE: To better discern the prognostic significance of estrogen-progesterone (ER-PR) receptor proliferative index, tumor suppressor gene, and over expression of oncogene c-erbB-2 in correlation with survival time and recurrence of tumor. MATERIAL AND METHOD: Paraffin blocks from 65 cases of endometrial carcinoma diagnosed and treatment at Rajavithi Hospital, Bangkok, Thailand with a follow-up time of at least 60 months were immunohistochemical studiedfor ER and PR status, tumor proliferative index (Ki-67), tumor suppressor gene (p53), and overexpression of oncogene c-erbB-2. Survival analysis was performed with the Cox proportional hazards. RESULTS: The mean age of the patients was 54.94 years with a range of 24 to 80 years. The mean follow-up time was 50.35 months. Nine patients (13.8%) had recurrent tumors, 5 years after treatment. Ten patients (15.4%) died of the primary disease during the follow-up period. ER was positive in 50 cases (76.9%) and negative in 15 cases (23.1%). PR was positive in 47 cases (72.3%) and negative in 18 cases (27.7%). Both ER and PR showed significant correlation (p<0.01). Ki-67 showed 27 cases (41.5%) having >35% positive nuclear staining and 38 cases (58.5%) had < or =35% positive nuclear staining. p53 was positive in 31 cases (47.7%) and negative in 34 cases (52.3%). c-erbB-2 was positive in one case (1.5%), equivocal in six cases (9.2%), and negative in 58 cases (89.3%). CONCLUSION: Survival analysis showed that cases with low-stage, low-grade, no recurrent tumor, ER and PR positive, and Ki-67 < or =35% had good survival compared to cases with high-stage, high-grade, presence of recurrent tumor, ER-PR-negative, and Ki-67 > 35% (p<0.05). Cox regression analysis showed ER-PR status and Ki-67 were significant independent prognostic indicators for survival time. Ki-67 expression was also a significant independent prognostic indicator for recurrent tumor p53 and c-erbB-2 displayed no statistical significance related to survival time.

Colorectal carcinomas from Middle East. Molecular and tissue microarray analysis of genomic instability pathways

To evaluate the overall incidence of microsatellite instability [MSI], hereditary non polyposis colorectal cancer, and tumor supressor gene [TP53] mutations in Saudi colorectal carcinomas. We studied the MSI pathway in Saudi colorectal cancers [CRC] from 179 unselected patients using 2 methods: MSI by polymerase chain reaction, and immunohistochemistry detection of mutL homologs 1 and mutS homologs 2 proteins. The TP53 mutations were studied by sequencing exons 5, 6, 7, and 8. Of the 150 colorectal carcinomas analyzed for MSI, 16% of the tumors showed high level instability [MSI-H], 19.3% had low-level instability [MSI-L] and the remaining 64% tumors were stable. Survival of the MSI-H group was better as compared to the MSI-L or microsatellite stable group [p=0.0217]. In the MSI-H group, 48% were familial MSI tumors, which could be attributable to the high incidence of consanguinity in the Saudi population. The TP53 mutations were found in 24% of the cases studied. A high proportion of familial MSI cases and a lower incidence of TP53 mutations are some of the hallmarks of the Saudi colorectal carcinomas, which need to be explored further

Prognostic significance of Bcl-2, Bax and p53 expression in breast cancer

Aim: of this study was to investigate the significance of apoptosis-related genes bcl-2 and Bax in breast carcinoma cases treated with radical surgery plus radiotherapy and adjuvant chemotherapy for at least 1 year and their relation with expression of p53

Methods: After surgical resection imunohistochemistry was performed to determine Bcl-2, Bax, p53 and estrogen receptor [ER] expression in paraffin-embedded tissues of 50 invasive breast cancers. And overall survival was assessed

Results: Bcl-2, Bax, P53 and ER immunostaining displayed a positive relation with increasing histologic grade [P=0.000] and negative relation with time staging. Bcl-2 displayed a negative relation with p53 [P=0.035] and a positive relation with Bax and ER [P= 0.003 and P= 0.011 respectively]. Expression of Bc12 was associated significant improvement in overall survival [P=0.01]

Conclusion: regulation of apoptosis is important in invasive ductal carcinoma. These results indicate that bcl-2 expression is significantly associated with hormonal receptor status so it is good prognostic marker, and that p53 is a significant prognostic marker. No significant relation between Bax and overall survival in relation to the stage, p53 or ER

Study of angiogenesis, P53 and NM23 expression in colorectal carcinoma

Colorectal carcinoma [CRC] is not uncommon in Egypt. Sustained angiogenesis is characteristic of several pathological conditions including tumor growth. Many researches were conducted to investigate the role of P53 in colorectal carcinogenesis; also the role of NM23 in tumor progression and for metastasic potential is not so clear in CRC. In this research we are aiming to study the pattern and density of angiogenesis in colorectal carcinomas, in addition to other histopathological prognostic factors. Besides we are also aiming to study the expression of P53 and NM23 and the relation between these three factors [Angiogenesis, P53 and NM23] in different grades and stages of colorectal carcinomas. The study comprised 44 resection specimens of colorectal carcinomas collected from specimens of department of pathology, Faculty of Medicine, Tanta University Hospital and from same of the private laboratories. Each block was stained by hematoxylin and eosin [H and E], immunohistochemical stain for CD34, VEGF, P53 and NM23. Histopathological assessment of grading was done according to WHO classification and staged according to TNM classification. The present study includes 44 cases of colorectal adenocarcinoma 35 were male patients and 9 cases were females. The age range was 20 to 80 years. The patients were grouped into three groups as follows: Group [1]: CRC without nodal or distant metastasis, group [II]: CRC with nodal but no distant metastasis and group [III]: CRC with distant metastasis. Most of the tumors were conventional invasive adenocarcinomas, on studying angiogenesis we found that the relation of microvascular density [MVD] detected by CD34 was not significant with the tumor size. Besides there were a significant results between the microvascular density and metastatic history of the disease. There were significant results between VEGF expression and the studied variables. The study ol apoptosis using P53 reveals significant relation between it and the studied variables but not with the nodal or blood metastasis, there was an inverse relation between NM23 and both VEGF and P53, but the results was not significant with the tumor grade and size, so in the present study the relation between VEGF, P53 and NM23 was significant but each marker have its own variable result with the grade .size and the stage of the tumor. In the present study it can be concluded that MVD at vascular hot spots is a very important predictive factor in CRC in addition to VEGF .P53 over expression has an impact on the biological behavior of CRC being more expressed in biological aggressive tumors and it has a role in angiogenicStudy of Angiogenesis, P53 and NM23 Expression in Colorectal Carcinoma activity of the tumor. We also concluded that NM23 is an important metastatic suppressor gene in CRC. So NM23, P53, VEGF and MVD by CD34 all are important to predict the outcome of the disease and they can be used as a guide for treatment. MVD, microvascular density; VEGF, vascular endothelial growth factor; CRC, colorectal carcinoma

p53 Genetic Polymorphism of Gastric cancer in Korea

BACKGROUND: Deletion or functional loss of the p53 tumor suppression gene plays a role in oncogenic transformation. The codon 72 polymorphism on exon 4 in the p53 gene produces variant proteins with either arginine (Arg) or proline (Pro), and is associated with an increased susceptibility of cancers of the lung, esophagus, breast, cervix and nasopharynx on a genetic basis. We designed this study to evaluate the influence of the p53 codon 72 polymorphism on gastric cancer in Korea. METHODS: We extracted the peripheral blood samples in 84 patients with gastric cancer, 66 patients with H. pylori-associated chronic gastritis and 43 controls without H. pylori infection. PCR-RFLP analysis was performed to detect p53 codon 72 polymorphism in these patients. RESULTS: There was no specific genotype of p53 polymorphism in the gastric cancer group compared to the other groups and no difference in genotypes by histologic subtypes. Classified by tumor location, Pro/Pro genotype was associated with an increase in proximal cancer and Arg/Arg genotype with distal cancer. As the frequency of p53 Arg allele increased, the cancer was of a more poorly differentiated type. CONCLUSIONS: The specific genotype of p53 polymorphism seems to correlate with tumor location. Increased frequency of p53 Arg allele is associated with more poorly differentiated cancers.

Immunohistochemical analyses of P53, cyclin D1, RB1, C-fos and N-ras genes expression in hepatocellular carcinoma in Iran

Hepatocellular carcinoma is the most common primary malignant tumor of the liver. The effect of some genes especially those involved in cell cycle regulation have been shown in the development of this cancer in several studies but there are some controversies about them yet.The paraffin-embedded tissue samples of 25 patients [18 males and 7 females] with hepatocellular carcinoma were collected from 22 pathology centers in Tehran during a period of 2 years [2000-2001]. Using immunohistochemistry method [avidin-biotin-peroxidase], they were stained for detection of p53, cyclin D1, RB1, c-fos and N-ras proteins.The mean [ +/- SD] age of the subjects was 60.56 +/- 12.52 years. Six [24%], 5[20%], 12[48%] and 2[8%] were positive for p53, cyclin D1, C-fos and N-ras, respectively. Twenty-two [88%] samples had alterations in the G1 cell-cycle checkpoint proteins [RB1 or cyclin D1]. P53 positive cases showed a higher [9 times] risk of being positive for RB1 gene comparing with p53 negative samples. RB1 loss of expression in association with p53 over-expression has been observed in 4[66.7%] of samples. Loss of expression of RB1 was seen in all cyclin D1 positive, 20[90.9%] N-ras negative, and 11[50%] C-fos positive cases. Comparing cyclin D1 positive cases with the negative ones, the former group showed a higher [2.85 and 4.75 times] risk of being positive for c-fos and N-ras genes.The development of mutation in p53, RB1 and c-fos genes appear to have a key role in the carcinopathogenesis of HCC in Iran. Also a significant association between simultaneous mutations of these genes during development of HCC is likely

Mutation and overexpression of p53 as a prognostic factor in canine mammary tumors

We concentrated ourselves to evaluate the prognostic significance of the p53 gene mutations, its protein expression and MIB-1 index as a proliferative marker in canine mammary tumors. In the present study, a total of 20 cases were examined, among which there were 5 malignant mixed tumors, 4 mammary gland adenocarcinomas, 1 papillary adenocarcinoma, 8 benign mixed tumors and 2 mammary gland adenomas. Positive immunostaining for p53 with PAb240 antibody was found in 2 benign (20%) and 3 malignant (30%) tumors. However, PAb421 antibody did not give positive result at all. In Western blot analysis, the p53 expression in benign and malignant tumors was detected in 4 and 3 cases, respectively. p53 mutations were found in 6 cases out of the cases with detected p53 protein expression. The MIB-1 index in benign and malignant tumors were 17.6+/-20.8% and 29.0+/-27.2%, respectively and there was no significant difference between tumor types. There was a significant correlation between p53 mutations and p53 overexpression (correlation coefficient = 0.5, p < 0.05). In Kaplan-Meier survival analysis, the p53 index was associated with significantly shortened survival time (p < 0.01). In multivariate analysis, p53 overexpression was only an independent factor for indicator of worse prognosis in canine mammary tumors (p = 0.01). These results demonstrated that p53 gene mutations and protein overexpression using the PAb240 anti-p53 antibody were useful predictors of increased malignant potential and poor prognosis in canine mammary tumors.

p53 aberrations in oral sub mucous fibrosis and oral cancer detected by immunohistochemistry.

Study of expression of p53 oncoprotein in several precancerous and cancer have been done, but only one literature is available regarding p53 expression in Oral Sub Mucous Fibrosis (OMSF), hence this study was taken up (i) to determine the expression of aberrant p53 in Oral Sub Mucous Fibrosis (OSMF) and Oral Squamous cell carcinoma (SCC) patients. (ii)To study correlation if any between p53 expression and degree of dysplasia in OSMF and SCC patients and (iii)To study correlation if any between p53 expression and habits in OSMF and SCC patients. Study Design consists of biopsy specimens of 38 cases of OSMF and 37 cases of Squamous cell carcinoma were subjected for staining by immunohistochemistry for p53 protein using LSAB visualization system kit. Clinical details along with habits were recorded and the data analyzed with t- test and chi- square test. Results of the study reveals 18 cases of OSMF and 26 cases of SCC were positive for p53 protein. Only 4 cases of SCC showed (++)grade and the rest all had (+)grade. Out of 75 patients, 65 had the habit of smoking and chewing, 4 patients history of habit was not known. Among patients with habits (65), 40 specimens were +ve for p53 stain and 2 out of 6 without history of habit, 2 out of 4 unknown history of habit took up p53 stain. To conclude study showed higher percentage of p53 positive cells in oral cancer cases when compared to oral sub mucous fibrosis cases. It suggests p53 expression may correlate with increase in dysplasia or malignant transformation. Both smoking and chewing habits had a significant role in p53 positive expression.

P53 tumor suppressor gene evaluation in ovarian cancer by DGGE based mutation scanning

Ovarian cancer remains the leading cause of death from gynecologic malignancy in western countries. This cancer results from a succession of genetic alterations involving oncogenes and tumor suppressor genes, which have a critical role in normal cell growth regulations. Forty-nine patients were studied for p53 mutations detection using combination of PCR amplification and DGGE which allows comprehensive mutation scanning for exons [5-8], mutation were confirmed by DNA gene sequencing. From 49 cases 5 cases showed mutation [10.2%] 3 mutations were detected in exon 6, one in exon 8, one in exon 5 [3] and all were point mutations. Of total mutations detected four were serous adenocarcinoma [4/24] [16.7%] and one was undifferentiated carcinoma. Detection of gene mutations by DGGE has proved to be a very accurate strategy

Mutations of p53 Tumor Suppressor Gene in Spontaneous Canine Mammary Tumors

Mutation of the p53 tumor suppressor gene has been related in the pathogenesis of numerous human and canine cancers, including breast cancers and mammary tumors. We have investigated exons 5-8 of the p53 gene for mutations in 20 spontaneous canine mammary tumors using polymerase chain reaction (PCR) with direct sequence analysis to evaluate the role of this gene in canine mammary tumorigenesis and analyzed to compare with other clinicopathological parameters including age, histology, stage, recurrence and death from tumor. Four missense (one case had two missense mutations) and one nonsense mutations were detected in 10 malignant lesions (40%), and two missense and one silent mutations were found in 10 benign mammary tumors (30%). Five of the missense mutations were located in highly conserved domains II, III, IV and V. After a follow-up period, four dogs showed a progression and three of these patients revealed death from mammary carcinoma with p53 mutation. These results demonstrated that the p53 gene mutations might be involved in the development of canine mammary tumors and contribute to the prognostic status in canine mammary carcinomas.

Low frequency of p53 mutations in cervical carcinomas among Brazilian women

Human papillomavirus (HPV) infections of the high-risk types are strongly linked to the development of cervical carcinoma. The HPV oncoproteins E6 and E7 are thought to play a crucial role in this process through their interactions with the p53 protein and the retinoblastoma susceptibility gene product pRb, respectively. E6 binds to p53 protein promoting its degradation. This is considered to contribute to the oncogenesis of HPV-associated anogenital cancer. On the other hand, in HPV-negative cervical carcinoma, p53 mutations are thought to have a role in the transformation process. A total of 122 HPV-positive cervical carcinoma tissue samples were evaluated for the presence of mutations in exons 5-8 of the p53 gene by single-stranded conformation polymorphism analysis and DNA sequencing. Only four missense point mutations were detected. These findings suggest that other mechanisms independent of p53 inactivation may play a role in the genesis of cervical carcinomas.

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

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