Ki-ras codon 12 point mutational activation in Hong Kong colorectal carcinoma patients

Ko, Josephine Mun Yee; Cheung, Michael; Wong, Chow-Ming; Lau, Kwok-Wai; Tang, Cecilia Man-Ching; Kwan, Ming Wa; Lung, Maria Li

doi:10.1016/s0304-3835(98)00257-2

Cited by 12 publications

(5 citation statements)

References 15 publications

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“…The incidence of K-ras genes in advanced colorectal carcinomas depends on characteristics of individual patients. There is only limited information available for Asia, but a Hong Kong report demonstrated a 30% genetic incidence of K-ras mutation (21) and a Singapore study generated a value of 28%, both of which are relatively low and in line with our findings. The fact that one comparison study between 1962 -1966 and 1994 -1996 in Singapore resulted in incidence rates of 0% and 28%, respectively, (22) suggests that an increased frequency of K-ras mutations might be characteristics not only of Japan but also other westernizing countries.…”

Section: Discussionsupporting

confidence: 88%

Increase in the frequency of K‐ras codon 12 point mutation in colorectal carcinoma in elderly males in Japan: The 1990s compared with the 1960s

et al. 2005

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Section: Discussionsupporting

confidence: 88%

Increase in the frequency of K‐ras codon 12 point mutation in colorectal carcinoma in elderly males in Japan: The 1990s compared with the 1960s

et al. 2005

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“…The proximal location of tumors in African Americans is consistent with the tumors in Western and Asian studies [ 31 - 33 , 46 , 47 ] which may reflect the impact of western diets on the African Americans. However, the high MSI level for African Americans for this limited sample size may in part be due to the increased age of these patients along with finding the majority of the tumors on the right side of the colon.…”

Section: Discussionsupporting

confidence: 80%

Impact of BRAF, MLH1 on the incidence of microsatellite instability high colorectal cancer in populations based study

et al. 2008

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We have identified an alternative pathway of tumorigenesis in sporadic colon cancer, involving microsatellite instability due to mismatched repair methylation, which may be driven by mutations in the BRAF gene (V600E). Colorectal cancer (CRC) is the most common cancer in the world, and African Americans show a higher incidence than other populations in the United States. We analyzed sporadic CRCs in Omani (of African origin, N = 61), Iranian (of Caucasian origin, N = 53) and African American (N = 95) patients for microsatellite instability, expression status of mismatched repair genes (hMLH1, hMSH2) and presence of the BRAF (V600E) mutation. In the Omani group, all tumors with BRAF mutations were located in the left side of the colon, and for African Americans, 88% [7] of tumors with BRAF mutations were found in the right side of the colon. In African Americans, 31% of tumors displayed microsatellite instability at two or more markers (MSI-H), while this rate was 26% and 13% for tumors in the Iranian and Omani groups, respectively. A majority of these MSI-H tumors were located in the proximal colon (right side) in African American and Iranian subjects, whereas most were located in the distal colon (left side) in Omani subjects. Defects in hMLH1 gene expression were found in 77% of MSI-H tumors in both African Americans and Iranians and in 38% of tumors in Omanis. BRAF mutations were observed in all subjects: 10% of tumors in African Americans (8/82), 2% of tumors in Iranians (1/53), and 19% of tumors in Omanis (11/59). Our findings suggest that CRC occurs at a younger age in Omani and Iranian patients, and these groups showed a lower occurrence of MSI-H than did African American patients. Our multivariate model suggests an important and significant role of hMLH1 expression and BRAF mutation in MSI-H CRC in these populations. The high occurrence of MSI-H tumors in African Americans may have significant implications for treatment, since patients with MSI-H lesions display a different response to chemotherapeutic agents such as 5-fluorouracil.

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“…Table II summarizes the detection of multiple mutations in p53 , Ki‐ ras , Apc , Dcc and Mcc in the current group of Hong Kong Chinese CRC patients. p53 mutation frequencies for this group of patients of 35.4% (35/99) (Leung et al , 1997) and Ki‐ ras mutation frequencies of 30.3% (30/99) (Ko et al , 1998) have been reported previously. Tumors from 46 patients contained a minimum of 2 genetic alterations: 25 of these patients had 2, 15 patients had 3, 5 patients had 4 and 1 patient had 5.…”

Section: Resultssupporting

confidence: 66%

Genomic instability and alterations inApc,Mcc andDcc in Hong Kong patients with colorectal carcinoma

Cheung

Kwan

et al. 1999

Int. J. Cancer

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Our aim was to reveal the significance of tumor‐suppressor genes and genomic instability in 99 Hong Kong Chinese colorectal carcinoma (CRC) patients by PCR‐LOH analysis and PCR‐PTT assay. The frequencies of allelic loss of Apc, Mcc and Dcc and of APC truncation were 31.3% (15/48), 11.6% (5/43), 44.4% (20/45) and 46/93 (49.5%), respectively. The frequency of Apc LOH was similar to, the Mcc LOH was lower than, and the Dcc LOH was higher than that reported for Caucasians and Japanese. In Hong Kong CRC patients, the replication error‐positive (RER+) phenotype occurred with a frequency of 10% (10/99), which was similar to other results using microsatellite markers where RER+ frequencies ranged from 11% to 28%. The rates of genetic alteration in RER+ tumors were lower in tumors harboring p53, Mcc and Dcc alterations; similar in Apc; and higher in Ki‐ras tumors compared with RER– tumors, though these differences did not achieve statistical significance. None of the biomarkers examined were predictive of survival independently, but strong trends confirming earlier observations of associations between RER+ phenotypes with proximal tumor location and poorly differentiated tumor status were noted. The RER+ phenotype was correlated significantly to the less aggressive Duke's stage B and improved prognosis. Additionally, tumors with RER+ phenotypes were positively correlated with young age and sex. Our results support the observation that a subset of younger male CRC patients in Hong Kong may develop CRC via the RER pathway and show differences in RER status and sex. A significantly higher percentage of older Hong Kong Chinese CRC patients had APC truncations. Int. J. Cancer (Pred. Oncol.) 84:404–409, 1999. © 1999 Wiley‐Liss, Inc.

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Ki-ras codon 12 point mutational activation in Hong Kong colorectal carcinoma patients

Cited by 12 publications

References 15 publications

Increase in the frequency of K‐ras codon 12 point mutation in colorectal carcinoma in elderly males in Japan: The 1990s compared with the 1960s

Increase in the frequency of K‐ras codon 12 point mutation in colorectal carcinoma in elderly males in Japan: The 1990s compared with the 1960s

Impact of BRAF, MLH1 on the incidence of microsatellite instability high colorectal cancer in populations based study

Genomic instability and alterations inApc,Mcc andDcc in Hong Kong patients with colorectal carcinoma

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