Mutation of Ki-ras and N-ras oncogenes in myelodysplastic syndromes

Lyons, John F.; Janssen, J. W. G.; Bartram, CR; Layton, Mark; Mufti, GJ

doi:10.1182/blood.v71.6.1707.bloodjournal7161707

Cited by 9 publications

(10 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These results support the heterogeneous nature of IPMT cells and suggest that the degree of heterogeneity may progress as the tumor advances. Lyons et al 19 concluded that ras mutations in myelodysplastic syndromes were heterogeneous and suggested that they may occur at an early stage of carcinogenesis. Lyons et al further suggested that ras mutations might be useful as a clonal marker for studying myeloid malignancies.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Comparison of K‐ras point mutation distributions in intraductal papillary‐mucinous tumors and ductal adenocarcinoma of the pancreas

Kitago

Ueda

Aiura

et al. 2004

Intl Journal of Cancer

View full text Add to dashboard Cite

Intraductal papillary-mucinous tumors (IPMT) consist of cells with varying histologic degrees of severity and exhibit multiple tumor loci; however, whether or not these lesions exhibit the same genetic changes has not been clarified. To investigate this point, we analyzed K-ras mutations in multiple IPMT lesions from each patient enrolled in our study and compared our findings to those for patients with ductal adenocarcinoma of the pancreas (DC). Twenty IPMT specimens and 7 DC specimens were resected, microdissected and analyzed for the presence of K-ras mutations. The mutated genes were then sequenced using a genetic analyzer. K-ras mutations were observed in 80% of IPMT and 100% of DC patients. More than 2 types of K-ras mutation were observed in the main tumors of 43.8% of IPMT and 0% of DC patients. K-ras mutations in peritumoral and separated lesions were observed in 66.7% and 62.5% of IPMT patients, respectively. At least one identical mutation between the main tumor and the peritumoral or separated lesions was recognized in all of the IPMT patients with those lesions. Different mutations from those in the main tumor were observed in 40% of IPMT patients with separated lesions. The survival curve of IPMT-carcinoma patients with more than 2 types of K-ras mutation in the main tumor was better than that with one type of K-ras mutation. IPMT patients exhibit a remarkably genetic heterogeneity in main tumor and have good prognosis. © 2004 Wiley-Liss, Inc. Key words: intraductal papillary-mucinous tumors; postoperative survival rate; microdissection; non-RI SSCP; heterogeneityIntraductal papillary-mucinous tumor (IPMT) of the pancreas is a relatively new tumor classification that has been the topic of an increasing number of reports. IPMT is associated with the massive dilatation of the pancreatic duct and its branches by the copious production of mucin. IPMT was first described by Ohhashi et al. 1 in 1982 as a "mucous-secreting pancreatic cancer." This entity has since been reported not only in Japan, 2-4 but also in Europe and the United States 5-8 under a variety of names. The term IPMT has been adopted by the World Health Organization's International Histological Classification of Tumors. 9 IPMT can be further classified as a benign adenoma, a moderate dysplasia (borderline) or a carcinoma (noninvasive or invasive), but reliably distinguishing one type from another is difficult to perform preoperatively, and all IPMTs are suspected of having malignant potential. 6 -8 Compared to ductal adenocarcinoma (DC) of the pancreas, IPMT clearly has a more favorable natural history characterized by a much longer survival period and a much higher cure rate. [5][6][7][8] Inasmuch as various oncogenes are now known to be involved in the pathogenesis of cancer and of pancreatic carcinomas in particular, the lower incidence of malignancy and the reduced aggressiveness of IPMT compared to DC may be the result of a different spectrum of genetic changes. K-ras mutation, a type of mutation that is frequently detected in pan...

show abstract

Section: Discussionmentioning

confidence: 99%

“…K‐ras mutations have been recently shown to occur at a relatively early stage of multistep carcinogenesis in pancreas lesions. These mutations have also been used as a clonal marker in myelodysplastic syndromes 19…”

mentioning

confidence: 99%

Comparison of K‐ras point mutation distributions in intraductal papillary‐mucinous tumors and ductal adenocarcinoma of the pancreas

Kitago

Ueda

Aiura

et al. 2004

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…Mutations in the ras family genes have also been detected in patients with myelodysplastic syndromes (101), at significant frequency. However, the presence of the mutation was not associated with the development of acute leukemia (AL), indicating that this particular aberration in the ras genes could not serve as a prognostic factor (101,102). Vashiukin et al (103) detected activated N-ras alleles in the blood plasma of patients with AL or myelodysplasia syndrome (MDS) and proposed that plasma could be a useful material for monitoring myeloid disorders.…”

Section: Mutations Of Ras Genes By Sitementioning

confidence: 99%

Mutations of Ras Genes in Human Tumors (Review)

Kiaris¹,

Spandidos²

1995

Int J Oncol

109

107

View full text Add to dashboard Cite

Ras family genes (H-, K-and N-ras) are implicated in a wide range of human tumours. Mutations are a major activating mechanism for the ras family genes, mainly in codons 12, 13 and 61, resulting in their conversion from proto-oncogenes to activated oncogenes. The detection of mutant ras alleles in human tumours has been performed by several investigators in a wide range of tissues. The aim of our review was to summarize the data obtained from these studies and to investigate whether the presence of mutant ras alleles was associated with particular clinical parameters. Contents 1. Introduction 2. Methods of detection 3. Mutations of ras genes by site 4. Alternative methods of activation for the ras family genes 5. Conclusions and perspectives

show abstract

“…Upregulation of survivin appears to be an important activity of H‐RAS oncoprotein and a RAS/survivin axis regulates survival and proliferation of transformed hematopoietic cells independent of hematopoietic growth factors (6, 7). Since mutations of RAS are observed with relatively high frequency in CMML (38), survivin overexpression in this disorder may be caused by intrinsic dysregulation of its expression, possibly induced by RAS mutations or by constitutive activation of other signal transduction pathways (39, 40).…”

Section: Discussionmentioning

confidence: 99%

Survivin expression, apoptosis and proliferation in chronic myelomonocytic leukemia

Invernizzi¹,

Travaglino²,

Benatti³

et al. 2006

European J of Haematology

View full text Add to dashboard Cite

We analyzed the expression of the inhibitor of apoptosis survivin by immunocytochemistry in bone marrow cells from patients with chronic myelomonocytic leukemia (CMML) to evaluate possible abnormalities in comparison with other myelodysplastic (MDS) and myeloproliferative syndromes, and to investigate a possible correlation between survivin expression and altered apoptosis or proliferation, or relevant laboratory and clinical findings. Thirty-four patients with CMML [18 MDS-CMML and 16 myeloproliferative disorder (MPD)-CMML], 90 with MDS, 41 with acute myeloid leukemia (AML), 19 with chronic MPD and 25 control subjects were studied. In normal samples survivin was never detectable. In CMML survivin levels higher than in MDS and AML (P < 0.0001), but similar to those found in MPD were observed. In CMML and MDS apoptosis was significantly higher compared to normal controls and all other subtypes of leukemias (P < 0.0001). Proliferation did not differ significantly in normal controls, MDS and CMML; the lowest levels were observed in AML and MPD (P < 0.0001). In CMML there was no correlation between survivin expression and blast cell percentage, apoptosis or proliferation, FAB or WHO subgroup. Proliferation was higher in MDS-CMML and tended to correlate with overall survival. CMML-2 cases with higher survivin expression showed higher evolution rate and shorter survival. In conclusion, CMML is characterized by high proliferation and apoptosis. Survivin overexpression, by disrupting the balance between cell proliferation/differentiation and apoptosis, may play an important role in its pathophysiology. The detection of survivin-deregulated expression may provide a useful tool for diagnosis, prognosis and a possible target for experimental treatments.

show abstract

Mutation of Ki-ras and N-ras oncogenes in myelodysplastic syndromes

Cited by 9 publications

References 0 publications

Comparison of K‐ras point mutation distributions in intraductal papillary‐mucinous tumors and ductal adenocarcinoma of the pancreas

Comparison of K‐ras point mutation distributions in intraductal papillary‐mucinous tumors and ductal adenocarcinoma of the pancreas

Mutations of Ras Genes in Human Tumors (Review)

Survivin expression, apoptosis and proliferation in chronic myelomonocytic leukemia

Contact Info

Product

Resources

About