K-ras-2 G-C and G-T transversions correlate with DNA aneuploidy in colorectal adenomas

Giaretti, Walter; Pujić, Natalija; Rapallo, Arnaldo; Nigro, Stefano; Vinci, Angela Di; Geido, Elio; Risio, Mauro

doi:10.1016/0016-5085(95)90201-5

Cited by 48 publications

(62 citation statements)

References 29 publications

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“…24 -27 K-ras2 mutations in colorectal adenomas were detected in both DNA diploid and aneuploid cells and in some cases in regions of histologically normal mucosa, suggesting that K-ras2 mutations occur before change in DNA ploidy. 22,23 Also, human colorectal aberrant crypt foci, suggested to be early precursor lesions of adenomas, were found to be mutated in K-ras2 up to the 85% level. 28 -30 The present study addresses the possible relationship of specific Kras2 mutations with DNA aneuploidy and proliferation in human sporadic colorectal adenomas.…”

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confidence: 99%

Specific K-ras2 Mutations in Human Sporadic Colorectal Adenomas Are Associated with DNA Near-Diploid Aneuploidy and Inhibition of Proliferation

Giaretti

Rapallo

Geido

et al. 1998

The American Journal of Pathology

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Recent studies indicate that p21ras proteins mediate their multiple cell functions through interactions with multiple effectors and that the number of new effectors is growing. We recently reported that K-ras2 mutations in human colorectal adenomas were associated with chromosome instability and proliferation changes. In the present study , we extend these previous observations. Hereditary and multiple (n > 5) adenomas and adenomas with early cancer were excluded. Dysplasia was moderate in 91 cases and high in 25, and the median adenoma size was 1.5 cm. K-ras2 spectrum analysis was done by sequence-specific oligonucleotide hybridization using nuclear suspensions provided by analysis and sorting of multiparameter flow cytometry. In particular , tissue inflammatory cells were separated for DNA diploid tumors, whereas DNA aneuploid epithelial subclones were analyzed separately. K-ras2 mutations and DNA aneuploidy were both detected in 29 of 116 (25%) cases. DNA aneuploid index was in the near-diploid region in the majority of cases. DNA aneuploidy was strongly associated with G3 C/T transversions. An association was also found between low S-phase values and G3 A transitions. These findings were confirmed using multivariate logistic regression analysis to account for the effects of size , dysplasia , site , type , age, and sex. These data suggest that specific K-ras2 mutations in a subgroup of human sporadic colorectal adenomas play a role in chromosome instability and, contrary to expectations , are associated with inhibition of proliferation. (Am J Pathol 1998, 153:1201-1209)Ras proteins participate at the plasma membrane level in transduction of diverse extracellular physiological signals that are thought to induce appropriate gene expression toward proliferation and differentiation. Ras proteins possess an intrinsic GTPase activity and alternate between activated and inactivated forms. The best-known Ras transduction mechanism is a pathway from receptor tyrosine kinases to transcription factors phosphorylated by mitogen-activated protein kinases. Mutations of the ras oncogenes result in constitutive signaling to downstream elements and are detected at high frequency in many types of human cancer.

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Specific K-ras2 Mutations in Human Sporadic Colorectal Adenomas Are Associated with DNA Near-Diploid Aneuploidy and Inhibition of Proliferation

Giaretti

Rapallo

Geido

et al. 1998

The American Journal of Pathology

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“…Many studies have examined the association of K-ras mutations with CRC (Bos et al, 1987;Forrester et al, 1987;Vogelstein et al, 1988;Bos, 1989;Burmer and Loeb, 1989;Vogelstein et al, 1989;Capella et al, 1991;Oudejans et al, 1991;Sidransky et al, 1992;Bell et al, 1993;Finkelstein et al, 1993a and b;McLellan et al, 1993;Urosevic et al, 1993;Breivik et al, 1994;Moerkerk et al, 1994;Morrin et al, 1994;Giaretti et al, 1995;Hasegawa et al, 1995;Hayashi et al, 1995;Ranaldi et al, 1995;Carpenter et al, 1996;Span et al, 1996;Villa et al, 1996). However, there are significant differences in reported frequencies of K-ras mutations in CRC (McLellan et al, 1993).…”

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confidence: 99%

“…A significant proportion of CRCs have mutations in the K-ras oncogene (Bos et al, 1987;Forrester et al, 1987;Vogelstein et al, 1988;Burmer and Loeb, 1989;Delattre et al, 1989;Fearon and Vogelstein, 1990;Capella et al, 1991;Oudejans et al, 1991;Offerhaus et al, 1992;Bell et al, 1993;Finkelstein et al, 1993a and b;McLellan et al, 1993;Peltomaki et al, 1993;Urosevic et al, 1993;Breivik et al, 1994;Moerkerk et al, 1994;Morrin et al, 1994;Tanaka et al, 1994;Giaretti et al, 1995;Span et al, 1996). We report a study using 301 DNA samples extracted from a colorectal tumour bank.…”

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confidence: 94%

“…The American Cancer Society estimated that in 1995 more than 130 000 new cases of CRC would be diagnosed in the USA and that there would be 54 900 deaths from the disease (American Cancer Society, 1995). CRC onset and its progression has been studied extensively at the molecular (Bos et al, 1987;Forrester et al, 1987;Vogelstein et al, 1988;Burmer and Loeb, 1989;Delattre et al, 1989;Kern et al, 1989;Vogelstein et al, 1989;Fearon and Vogelstein, 1990;El-Deiry et al, 1991;Oudejans et al, 1991;Houlston et al, 1992;Laurent-Puig et al, 1992;Offerhaus et al, 1992;Sharrard et al, 1992;Bell et al, 1993;Finkelstein et al, 1993a and b;McLellan et al, 1993;Peltomaki et al, 1993;Urosevic et al, 1993;Breivik et al, 1994;Dix et al, 1994;Moerkerk et al, 1994;Morrin et al, 1994;Tanaka et al, 1994;Giaretti et al, 1995;Laird et al, 1995;Lewis et al, 1996;Span et al, 1996) and genetic (Woolf et al, 1958;Macklin et al, 1960;Houlston et al, 1992;Zhao and Le Marchand, 1992;Peltomaki et al, 1993;Goldgar et al, 1994;Lewis et al, 1996) levels and there is a commonly accepted model relating tumour grade according to Dukes' stage (Dukes, 1932) to specific DNA changes …”

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confidence: 99%

“…Although there are many examples of nucleic acid changes having potential as tumour markers (Bos et al, 1987;Forrester et al, 1987;Vogelstein et al, 1988;Burmer and Loeb, 1989;Delattre et al, 1989;Kern et al, 1989;Vogelstein et al, 1989; Fearon and Vogelstein, 1990;Jones and Buckley, 1990;Capella et al, 1991;El-Deiry et al, 1991;Oudejans et al, 1991;Stork et al, 1991;Laurent-Puig et al, 1992;Offerhaus et al, 1992;Sharrard et al, 1992;Bell et al, 1993;Finkelstein et al, 1993a and b;McLellan et al, 1993;Urosevic et al, 1993;Breivik et al, 1994;Dix et al, 1994;Magewu and Jones, 1994;Moerkerk et al, 1994;Morrin et al, 1994;Tanaka et al, 1994;Giaretti et al, 1995;Laird et al, 1995;Span et al, 1996), their value as clinical tools in cancer diagnosis, staging or even screening needs to be demonstrated and two important criteria must be met. First, adequate supplies of nucleic acid must be extracted from the clinical material; second, robust and accurate methods of analysis are required.…”

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confidence: 99%

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The detection of K-ras mutations in colorectal cancer using the amplification-refractory mutation system

Fox

England²,

White³

et al. 1998

Br J Cancer

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Summary A total of 301 colorectal carcinoma (CRC) archival samples were analysed using the amplification-refractory mutation system (ARMS). Each sample was examined to determine the mutation status of codons 12 and 13 of the K-ras oncogene. The results from direct DNA sequence analysis carried out on 30 of the samples differed from the ARMS result in almost 50% of the cases as a result of the relative excess of wild-type to mutated DNA sequences. To assess the validity of the ARMS data, the polymerase chain reaction (PCR) was used to generate an amplicon from K-ras exon from 23 of the samples. The PCR amplicons were cloned and sequenced, and the DNA sequence analysis of the cloned material was in agreement with the ARMS results in all but one case. This case represented a tumour that exhibited a five-nucleotide reversed inversion. The cloned sequence data confirm the sensitivity and specificity of the individual ARMS reactions and that it is possible in certain cases to detect additional, more complex, sequence variations.

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EDITORIAL. THE CONCEPTUAL AND PRACTICAL IMPACT OF Ki-ras MUTATION IN COLORECTAL NEOPLASIA

Arends¹,

Bosman²

1996

J. Pathol.

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K-ras-2 G-C and G-T transversions correlate with DNA aneuploidy in colorectal adenomas

Cited by 48 publications

References 29 publications

Specific K-ras2 Mutations in Human Sporadic Colorectal Adenomas Are Associated with DNA Near-Diploid Aneuploidy and Inhibition of Proliferation

Specific K-ras2 Mutations in Human Sporadic Colorectal Adenomas Are Associated with DNA Near-Diploid Aneuploidy and Inhibition of Proliferation

The detection of K-ras mutations in colorectal cancer using the amplification-refractory mutation system

EDITORIAL. THE CONCEPTUAL AND PRACTICAL IMPACT OF Ki-ras MUTATION IN COLORECTAL NEOPLASIA

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