Stimulated human leukocytes cause activating mutations in the K-ras proto-oncogene

Jackson, Jan C.; Vollenweider, Maya; Hill, Jennifer; Rodriguez, Henry; Schwabacher, Alan W.; Mitra, Gopa; Kuo, Chao-Yu

doi:10.1038/sj.onc.1201118

Cited by 20 publications

(12 citation statements)

References 30 publications

(37 reference statements)

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“…It was reported that leukocyte-derived potent oxidants could cause k-ras oncogene activation, which is believed to play a critical role in the pathogenesis of many human malignancies. 26) In our studies, a significant association between RER and k-ras mutation (P<0.05) was found; four of five DLBL with RER had k-ras mutation. MSI might lead to accumulation of genetic aberrations such as k-ras mutations, causing progression of low grade to high grade lymphoma.…”

Section: Discussionsupporting

confidence: 51%

Microsatellite Instability and k‐ras, p53 Mutations in Thyroid Lymphoma

Takakuwa

Hongyo

Syaifudin

et al. 2000

Japanese Journal of Cancer Research

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Patho-epidemiological studies showed that thyroid lymphoma (TL) arises in inflammatory lesions of chronic lymphocytic thyroiditis (CLTH). Replication error (RER) is found in inflammatory lesions and associated cancer, suggesting that chronic inflammation could be a risk factor for neoplastic development through causing RER. To clarify whether RER is involved in the pathogenesis of TL, we examined the microsatellite instability (MSI) in 9 cases with CLTH and 19 with TL, including 10 diffuse large B-cell lymphoma (DLBL), 4 follicle center cell lymphoma, 3 marginal zone B-cell lymphoma of extranodal (MALT) type, and 2 lymphoplasmacytic type. Sixteen distinct microsatellite repeats were analyzed. Mutations of p53 and k-ras genes were also examined. When alterations at 2 or more microsatellite loci were judged as positive, only 5 DLBL cases exhibited MSI. The frequency of MSI in DLBL was significantly higher than that in other types of TL and CLTH (P < < < <0.05). Four of 19 cases (21.1%) showed point mutation of the k-ras gene. The k-ras mutations occurred in the cases with DLBL with RER, and four of five cases with RER had a k-ras mutation, indicating a close association between RER and k-ras mutation. p53 mutations were not found in the CLTH. Two of 19 TL cases showed mutations of p53 gene. There was no significant association between RER and p53 mutation. These findings indicate that genomic instability contributes to the progression of TL from low grade to high grade, but not to the development of low grade lymphoma in CLTH lesions.

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Section: Discussionsupporting

confidence: 51%

Microsatellite Instability and k‐ras, p53 Mutations in Thyroid Lymphoma

Takakuwa

Hongyo

Syaifudin

et al. 2000

Japanese Journal of Cancer Research

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“…In strong support of some or all of the codon 12 mutations in our study being due to ROS, a recent study showed mutation in vitro of human K-ras contained in a plasmid and exposed to hydroxylradical generating systems [stimulated neutrophil plus iron or purine plus xanthine oxidase (Jackson et al, 1997]. Of 14 mutants obtained in codon 12, seven were G to T, ®ve were G to A, and one was G to C, a pro®le very similar to that in our study.…”

Section: Discussionsupporting

confidence: 82%

“…Eects of ROS on expressed vs nonexpressed genes have not been reported as yet. Although inclusion of 8-oxo-dG in both H-ras and K-ras caused G to T and G to A changes, leukocytederived hydrogen peroxide was unable to induce these changes in H-ras (Jackson et al, 1997), con®rming the potential importance of secondary or tertiary chromatin structure for the interaction.…”

Section: Discussionmentioning

confidence: 95%

Selective mutation of K-ras by N-ethylnitrosourea shifts from codon 12 to codon 61 during fetal mouse lung maturation

et al. 1998

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“…Indeed, lymphocytes stimulated with phytohemagglutinin or antigen may release DNA (5 ). Furthermore, human leukocytes stimulated by neutrophil-derived hydroxyl radicals may cause activation of K-ras codon 12 (6 ). In addition, inhaled particles in exposed individuals can generate reactive oxygen species that can activate K-ras (7 ).…”

Section: To the Editormentioning

confidence: 99%