Cancer Research and Treatment

p53 Mutation of Head and Neck Squamous Cell Carcinoma Cell Lines: Chung Hwan Baek, Ye Jeung Ko, Young Ik Sun, Sung Wha Hong, Kwang Chol Chu; J Korean Cancer Assoc. 1998;30(1):12-19.

Abstract PDF: PURPOSE
Structural alterations of p53 and overexpression of the p53 protein are the most common genetic abnormalities in various kinds of human cancers. In this study, we examined the mutational status and the frequency of p53 mutations in head and neck squamous cell carcimona (HNSCC) cell lines.
MATERIALS AND METHODS
7 human head and neck squamous cell carcinoma cell lines were included in this analysis. Using polymerase chain reaction(PCR), single strand confonmation polymorphism(SSCP) and PCR-DNA sequencing analysis, we tested the mutational status of 7 cell lines. Exon 4~9 of the p53 gene was amplified for the direct DNA sequencing analysis.
RESULTS
Our results showed 100% nuclear p53 immunostaining and 3 electrophoretic abnomalities by PCR-SSCP in three cancer cell lines and mutations of the p53 gene including 2 base substitutions and 1 base deletion were detected in 3 cancer cell lines using PCR directed DNA sequencing analysis.
CONCLUSION
7 HNSCC cell lines examined in this study provide excellent systems for study of gene therapy using p53 gene.

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Mutation of K - ras Oncogene in Non - Small Cell lung Cancer: Choon Taek Lee, Keun Chil Park, Chang Min Kim, Jae Ill Zo, Young Mog Shim, Weon Seon Hong, Jhin Oh Lee, Taik Koo Yun; J Korean Cancer Assoc. 1994;26(1):100-106.

Abstract PDF: The mutations of K-ras oncogenes have been detected in about 20~30% of non-small cell lung cancer(NSCLC). In some reports K-ras activations are associated with smoking and poor prognosis in NSCLC patients who undergo curative resection. The ras oncogenes are usually activated by point mutations. The development of polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP) enables us to detect the subtle nucleotide changes such as point mutations. In SSCP the electrophoretic mobility of single strand nucleotide de- pends on not only its size but also its conformation determined by DNA sequences. We analysed genomic DNAs of 41 human NSCLC obtained by thoracotomy using PCR-SSCP of K- ras codon 12, 13 and K-ras codon 61, and compared the results with clinical informations. The electrophoretic mobility changes were found in 10 of 41 NSCLCs(24.4%) in K-ras codon 12, 13. Those changes were found in six of 25 squamous cell carcinomas(24% ) and four of 16 adenocarcinomas(25%). But no change was found in K-ras codon 61. Comparisans of clinical parameters including age, sex, stage, smoking, and survival showedno significant differences between two groups with or without K-ras mutation. These results suggest that the mutation of K-ras oncogene may play an important role in the pathogenesis of some group of NSCLC though the clinical significances of these molecular events are open to further investigations.

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Sequencing of p53 Gene Mutations in Primary Breast Cancer Tissues: Jeoung Won Bae, Bum Hwan Koo, Cheung Wung Whang, Seul Hee Park, In Sun Kim; J Korean Cancer Assoc. 1999;31(4):663-669.

Abstract PDF: PURPOSE
The etiology of breast cancer involves very complex factors such as genetic, hormonal, and dietary. The peak age of Korean breast cancer is much earlier, about ten years, than those of western countries. The role of p53 gene on the carcinogenesis has been studied since 1991. This study was designed for the evaluation of genetic factor by determining p53 gene mutations in Korean breast cancer.
MATERIALS AND METHODS
Mutation screening on p53 tumor suppressor gene was examined with PCR-SSCP and nucleotide sequencing technique from the genomic DNA extracted from the 27 fresh-frozen breast cancer tissues.
RESULTS
Mutations in p53 gene exon 5-7 were identified in 2 of 27 cases (7%). One had a missense mutation substituted gcg with ggg at codon 159, exon 5, and the other had a point mutation substituted tcc serine to tGc cysteine at codon 241, exon 7.
CONCLUSION
Point mutation of p53 gene in breast cancer seems to be the major defect found in Korean patients. It is necessary to perform further study in mutation of other exon 2, 4, 8, 9, and 11 of p53 gene to compare the genetic backgrounds of Korean breast cancer with those of westerns.

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Germline Mutations of BRCA1 Gene in Korean Breast and/or Ovarian Cancer Families: Yong Jin Won, Jae Hwan Oh, Xiao Hong Huang, Dong Young Noh, Kuk Jin Choe, Soon Beom Kang, Lee Su Kim, Man Su Noh, Nam Sun Paik, Dae Hyun Yang, Se Min Oh, Soon Nam Lee, Jae Gahb Park; J Korean Cancer Assoc. 1997;29(5):713-723.

Abstract PDF: PURPOSE
To understand the involvement of BRCA1 gene in Korean breast and/or ovarian cancer families.
MATERIALS AND METHODS
Germline mutations of BRCA1 gene were analyzed in 13 families which included 3 hereditary site-specific breast cancer families, 6 suspected breast cancer families, and 3 suspected breast-ovarian cancer family, and one Li-Fraumeni family by screening BRCA1 gene using single strand conformation polymorphism (SSCP) analysis on polymerase chain reaction (PCR) amplified genomic DNA and confirmed the results by sequencing.
RESULTS
Including one family with previously reported nonsense mutation of BRCA1 gene, we detected two mutations in unrelated families. One newly identified mutation was frame shift mutation resulting from TG deletion in codon 1701, which results in a truncated BRCA1 protein, at codon 1714.
CONCLUSION
The proportion of families who inherit the mutated BRCA1 gene seems to be small among Korean breast and/or ovarian cancer families.

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Germline Mutation of Rb1 Gene in Korean Retinoblastoma Patients: Ja Lok Ku, Young Suk Yu, Jae Gahb Park; J Korean Cancer Assoc. 1997;29(2):291-298.

Abstract PDF: PURPOSE
Retinoblastoma is an intraocular tumor occurring almost exclusively in young children. Germline mutations in the Rb1 gene confer hereditary predisposition to retinoblastoma. To identify germline mutations in the Rb1 gene in Korean retinoblastoma patients, we analyzed germline mutations of the Rb1 gene in 4 Korean retinoblastoma patients from 3 families.
MATERIALS AND METHODS
All patients were bilaterally affected in early childhood. First patient and second patient were same family members (SNU-RB1-1 and -2), and in the third patient (SNU-RB2), tumor cells had metastasized to the central nervous system 2 years after treatment of retinoblastoma. Fourth patient (SNU-RB3) developed secondary osteosarcoma in the nasal cavity 15 years after treatment of retinoblastoma. We have used PCR-SSCP analysis and DNA sequencing analysis to screen germline mutations.
RESULTS
We found one missense mutation in the fourth patient (SNU-RB3). This was a point mutation from AAA (lysine) to GAA (glutamine) at codon 616 in exon 19 of the Rb1 gene.
CONCLUSION
We confirmed one germline mutation of the Rb1 gene in one Korean patient who had a sporadic bilateral retinoblastoma and osteosarcoma. Identification of the germline mutation in Rb1 gene would help to improve the presymptomatic diagnosis and clinical management of retinoblastoma patients.

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Detection of p53 Gene Mutations in Gastric Cancers: Comparative study of Single Strand Conformational polymorphism migration Technique (SSCP) and Non-Isotopic RNase Cleavage Assay (NIRCA): Young Jin Kim, Ji Yun Kook, Ji Hee Lee, Hyeong Rok Kim, Jae Hwan Joo, Dong Yi Kim, Shin Kon Kim, Soon Pal Suh, Jin Pok Kim; J Korean Cancer Assoc. 1997;29(2):212-219.

Abstract PDF: PURPOSE
The aim of the present study was: (a) to determine the frequency of p53 mutations by single strand conformational polymorphism analysis of polymerase chain reaction products (PCR-SSCP), Non-Isotopic RNase Cleavage Assay (NIRCA) and immunohistochemical staining with monoclonal antibody; and (b) to compare the correlations among these methods.
MATERIALS AND METHODS
Abberations of the p53 gene in 24 primary gastric carcinomas were examined by PCR-SSCP, NIRCA and immunohistochemical staining. Of these surgically resected gastric adenocarcinomas, 23 were advanced gastric carcinomas and 1 was early gastric cancer. Using PCR-SSCP and NIRCA, the presence of mutations in exons 4-9 was evaluated. Using the mouse specific anti-human p53 monoclonal antibody, we also looked for overexpression of the p53 protein in tissue sections.
RESULTS
In 5 cases shifted bands were reproducibly identified by PCR-SSCP, and two mutations were identified in exon 4 and three in 5 & 6. The mutations of exon 4 were detected by NIRCA in 5 cases, exon 5 & 6 in 6 cases, and exon 7 in 2 cases. The p53 mutations detected by PCR-SSCP were also detected by NIRCA except one case. Thirteen of the tumor samples were positively stained with the monoclonal antibody for p53 protein. There was no correlation between p53 mutations detected by NIRCA and expression of p53 protein by immunohistochemical staining.
CONCLUSIONS
Our results in this group of patients suggest that NIRCA is more sensitive than PCR-SSCP in detecting p53 mutations, and expression of p53 protein by immunohistochemical staining does not directely represent the genetic changes of p53 gene.

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p53 Mutation in Gastric Carcinoma Detected by PCR - SSCP and Direct - Sequencing: Sang Suk Lee, Sang Pyo Kim, Eun Joo Sohn, Mi Seon Hwang, Soo Sang Sohn; J Korean Cancer Assoc. 1998;30(6):1069-1077.

Abstract PDF: PURPOSE
p53 gene mutations, one of the most common alterations found in human tumors, has also been detected in gastric carcinoma, and shown to have a crucial and early role in gastric carcinogenesis of intestinal type and mainly associated with tumor progression in the cancer of diffuse type. We tried to investigate the frequency of p53 mutations in 27 gastric carcinomas.
MATERIALS AND METHODS
Fresh tumor tissue from a series of gastric carcinoma was screened for p53 mutations by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) with silver staining and confirmed by direct-sequencing in 27 cases of gastric carcinoma. Immunohistochemical method for p53 protein accumulation was also performed in the same cases.
RESULTS
Immunohistochemistry revealed 20 of 27 cases of gastric carcinoma, positive for p53. PCR-SSCP analysis of p53 exons 5-8 detected mobility shift in 4 out of 20 p53-positive tumors; three from exon 5 and the other from exon 7, respectively. DNA sequencing of exon 5 showed CGC to CAC point mutation in one of three cases; exon 7, ATC to AAC point mutation. It seemed that there was no correlation between genetic alterations of p53 gene detected by PCR-SSCP and expression of p53 protein by immunohistochemistry. CONCLUSIOAS: Our results suggest that mutations of the p53 gene are rare genetic events in carcinogenesis of gastric carcinomas. There was discrepancy between mutations screened by PCR-SSCP and overexpressions in immunohistochemical staining.

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