Detection of codon 12 K- ras mutations in non-neoplastic mucosa from bronchial carina in patients with lung adenocarcinomas

Urban, T.; Ricci, Sylvie; Danel, Claire; Antoine, Martine; Kambouchner, Marianne; Godard, V; Lacave, Roger; Bernaudin, Jean-François

doi:10.1054/bjoc.1999.0935

Cited by 11 publications

(10 citation statements)

References 39 publications

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“…25 The same transition has been described in preneoplastic lesions, such as aberrant crypt foci (ACF) in the colon, 26 or even phenotypically normal mucosa located near neoplastic lesions, as in the case of nonneoplastic mucosa from bronchial carina in patients with lung adenocarcinomas. 27 In the present study, mutations were not observed in control tissues, including peripheral blood and phenotypically normal conjunctival specimens, harvested from the same patients, implying that the mutations detected may be specific for pterygium.…”

Section: Discussioncontrasting

confidence: 43%

Detection of point mutations at codon 12 of KI-ras in ophthalmic pterygia

Detorakis

Zafiropoulos

Arvanitis

et al. 2004

Eye

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Aims Ophthalmic pterygium is a potentially vision-threatening lesion of unknown etiology, related to an exposure to solar light. Mutations to the ras genes are frequently observed in lesions related to an exposure to solar light. The present study aims at screening pterygia for mutations at codons 12 and 13 of the ras genes. Methods In all, 50 pterygia were examined, together with respective blood samples and specimens of normal conjunctiva. A PCR reaction was performed to amplify sequences containing codons 12 and 13 of Ki-ras, H-ras, and N-ras. An RFLP analysis was then performed to detect point mutations at codon 12. The mutational status at codons 12 and 13 was further explored with sequencing of PCR products.Results RFLP analysis revealed Ki-ras mutations at codon 12 in five (10%) of pterygia, whereas H-ras or N-ras mutations were not observed. Sequencing confirmed Ki-ras mutations at codon 12 and revealed absence of mutations at codon 13. The presence of Ki-ras mutations was significantly correlated with postoperative recurrence (P ¼ 0.02) and young age (P ¼ 0.04). Mutations were not observed in specimens of blood or normal conjunctiva for any of the genes examined. Conclusions The absence of N-ras mutations is in agreement with previous reports concerning mucosal lesions. The detection of Ki-ras mutations and the association with postoperative recurrence implies a possible role of Ki-ras in the clinical profile of pterygium. The mechanism of Ki-ras mutations is unclear and could be independent of the action of UV light.

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Section: Discussioncontrasting

confidence: 43%

Detection of point mutations at codon 12 of KI-ras in ophthalmic pterygia

Detorakis

Zafiropoulos

Arvanitis

et al. 2004

Eye

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“…In another study, Clements et al (1995) analysed bronchoscopy specimens obtained from lung cancer patients and showed that K-ras mutations were found in both malignant and nonmalignant tissues in 22.7% (5 of 22) of the patients and in only nonmalignant tissue in 9.1% (2 of 22) of the patients. Finally, a recent study by Urban et al (2000) showed that K-ras mutations were detected in both lung tumour and bronchial carina tissue in 21% (4 of 19) of the patients, while being present only in the bronchial carina but not in the tumour in 11% (2 of 19) of the patients. These latter studies and our present study showed that K-ras mutations can be frequently found in non-neoplastic lung tissues, including histologically normal tissues.…”

Section: Figurementioning

confidence: 93%

“…Although K-ras mutations have been frequently found in lung tumours, the timing of their occurrence in the multistep process of lung carcinogenesis remains poorly understood. Such studies used tissue specimens removed at biopsy or resection (Sugio et al, 1992;Westra et al, 1993;Clements et al, 1995;Yakubovskaya et al, 1995;Urban et al, 1996;Keohavong et al, 1997b;Urban et al, 2000), and cell samples microdissected from embedded lung tissue sections (Sugio et al, 1994;Westra et al, 1996). Taken Topographic analysis of K-ras mutations in histologically normal lung tissues and tumours of lung cancer patients together, some of these studies suggest that K-ras mutations occur relatively late in lung cancer development (Sugio et al, 1994;Yakubovskaya et al, 1995;Urban et al, 1996), while other studies indicate that they could represent early events in this process (Li et al, 1994;Clements et al, 1995;Keohavong et al, 1997b;Urban et al, 2000).…”

mentioning

confidence: 99%

Topographic analysis of K-ras mutations in histologically normal lung tissues and tumours of lung cancer patients

Keohavong

Mady

Gao³

et al. 2001

Br J Cancer

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Mutations in the K-ras gene are very common in lung tumours and are implicated in the development of lung cancer, but the timing of their occurrence remains poorly understood. We investigated K-ras mutations in cell samples microdissected by laser capture microscopy at multiple sites from lung tissue sections representing tumour tissue and matched histologically normal tissue obtained from 48 lung cancer patients. K-ras mutations were detected in cell samples from 10 of 38 (26.3%) lung adenocarcinomas and in none of the histologically normal or tumour cell samples taken from 10 lung squamous cell carcinomas. Of the K-ras mutation-positive adenocarcinomas, in 4 cases a mutation was found in only the tumour tissue, in 1 case a mutation was found only in the histologically normal tissue, and in 5 cases mutations were found in both the tumour tissue and histologically normal tissue. Among these 5 cases, 2 had identical mutations in both the tumour tissue and histologically normal tissue, 2 had 1 mutation in the tumour tissue and 2 mutations in the histologically normal tissue, 1 of which was identical to the mutation found in the tumour, and 1 case had 2 codon 12 mutations in tumour tissue and 2 mutations, in codons 9 and 11, in histologically normal tissue. These results showed that K-ras mutations are frequent in histologically normal cells taken from outside lung adenocarcinomas and suggest that some of these mutations may represent early events which could pave the way of lung carcinogenesis. © 2001 Cancer Research Campaign http://www.bjcancer.com

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“…This may in turn explain the frequent simultaneous occurrence of KRAS mutations and alterations of the p16INK4A/p14ARF and/or p53 pathway in cancer cells, and suggests the occurrence of RAS mutations in an ordered multi-step manner during the carcinogenic process. Although there has been considerable controversy over whether KRAS mutations are present in pre-malignant or normalappearing lung tissues (Sugio et al, 1994;Urban et al, 2000), KRAS mutations are reportedly present in 25 -40% of AAH lesions (Westra et al, 1996;Cooper et al, 1997). Among the RAS family members, the KRAS gene is most frequently affected in lung cancers, usually at codon 12 Mills et al, 1995), while mutations of HRAS or NRAS are very rare (*1%) in lung cancers.…”

Section: The Ras Gene Familymentioning

confidence: 99%