From: "Dr. D. Kossove" <doctordee@telkomsa.net>
Subject: more about K-ras mutations in LMS and the vaccine trial in solid tumors
Date: Tuesday, January 20, 2004 10:12 AM

In terms of the solid tumor vaccine in clinical trial against K-ras mutations in solid tumors, here is some further information about K-ras in LMS.
If you are intererested in this NIH trial, your tumor would have to be tested for the K-ras mutations, probably by the NIH.    If you had the particular mutations, you would be a candidate for the trial if the other conditions were acceptable .   Look it up on PDQ clinical trials at the www.cancer.gov site .

doreen
Together we are more, and more effective, than we are separately.

All correspondence is my personal opinion.  I am not an oncologist.  I am not practicing medicine online.  Provision of information is for investigation and discussion with your doctors.


4: Cancer Epidemiol Biomarkers Prev. 1997 Dec; 6(12): 1095-100.  Related Articles, Links  


Detection of K-ras mutations in resected primary leiomyosarcoma.

Hill MA, Gong C, Casey TJ, Menon AG, Mera R, Gillespie AT, Giardina JF, Levine EA, Hunt JD.

Section of Surgical Oncology, Louisiana State University Medical Center, New Orleans 70112, USA.

Mutation of the K-ras oncogene occurs frequently in human malignancy. However, there are few reports concerning K-ras mutations in soft-tissue sarcoma, including leiomyosarcoma. We therefore designed a study to determine the prevalence of mutations in the first exon of K-ras in leiomyosarcoma and to evaluate its prognostic potential. Fifty-one leiomyosarcomas were reviewed, and their diagnoses were confirmed on pathological review. Tissue blocks were retrieved, and new sections were prepared for confirmation of diagnosis. Additional tissue sections were used for DNA isolation. PCR and denaturing gradient gel electrophoresis (DGGE) were used to detect K-ras mutations in the first exon of genomic DNA isolated from the specimens. Seven (14%) K-ras mutations were detected using DGGE. Subsequent sequencing of the K-ras gene from each of the mutated tumors confirmed the DGGE results in each case. The median survival for patients whose tumors did not contain mutations of K-ras was 42 months (n = 42) versus 25 months (n = 7) for those with mutations (P = 0.06). However, patients with stages I and II tumors had a median survival of 82 months (n = 28) compared to 28 months for those with stages III and IV disease (n = 20, P = 0.02). The results suggest that K-ras codon 12 mutations are uncommon in leiomyosarcoma; however, when such mutations are found, there is a trend toward worse survival. Furthermore, the data confirm that stage is a significant prognostic indicator.

PMID: 9419409 [PubMed - indexed for MEDLINE] 

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5: Mod Pathol. 1993 Mar; 6(2): 129-32.  Related Articles, Links  


H-ras-1 point mutations in soft tissue sarcomas.

Wilke W, Maillet M, Robinson R.

Department of Pathology, University of Iowa, Iowa City.

The H-ras-1 protooncogene is activated by single base substitutions occurring in either codon 12, 13, or 61. These mutations have been described with varying frequencies in several human tumor types. Since ras oncogenes were first discovered as the transforming sequences of Harvey and Kirsten murine sarcoma viruses (which also contain activating point mutations compared to the homologous cellular sequences), we wished to investigate the possibility that ras mutations might also occur in human sarcomas. We extracted DNA from six malignant fibrous histiocytomas (MFH), three embryonal rhabdomyosarcomas (ER), one alveolar rhabdomyosarcoma, one pleomorphic rhabdomyosarcoma, and one leiomyosarcoma. The DNA from regions flanking codons 12/13 and codon 61 was amplified by the polymerase chain reaction and sequenced with an automated DNA sequencer. As controls, we amplified and sequenced normal DNA (placenta) and DNA with known point mutations (T24 bladder carcinoma cells). We found three cases with mutations, all occurring in codon 12. One ER showed a G-to-T mutation in the second position of codon 12 (coding for valine instead of glycine). Two MFHs showed G-to-A mutations in the second position of codon 12 (coding for aspartic acid instead of glycine). Although a limited number of cases were sampled, we conclude that study of H-ras-1 mutations may be relevant to MFH and ER. Additional studies of N and K-ras mutations as well as more cases investigating H-ras will be required before we can ascertain the significance of ras mutations in the oncogenesis of human soft tissue sarcomas.

PMID: 8483882 [PubMed - indexed for MEDLINE] 

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6: Oncogene. 1991 Sep; 6(9): 1651-6.  Related Articles, Links  


Detection of transforming genes by transfection of DNA from primary soft-tissue tumours.

Gill S, Stratton MR, Patterson H, Spurr NK, Fisher C, Gusterson BA, Cooper CS.

Section of Molecular Carcinogenesis, Institute of Cancer Research, Sutton, Surrey, UK.

A series of adult soft-tissue tumours were screened for the presence of activated oncogenes by transfecting tumour DNA into NIH3T3 mouse fibroblasts. In these studies an activated K-ras gene that contained a mutation at the second position of codon 12 (GGT----GAT) was found in a leiomyosarcoma. In addition, following transfection of DNA from a liposarcoma, we identified an activated gene that failed to hybridize to probes prepared from 10 known human oncogenes (K-ras, H-ras, N-ras, ret, met, trk, mas, dbl, raf and hst) that have previously been detected in DNA transfection experiments. BamHI-BamHI fragments of this activated gene of 3.5 and 8.5 kb were cloned from NIH3T3 secondary transfectants using a probe that detects the human alu family of highly repetitive DNA sequences. Repeat-free subclones of these BamHI fragments were used to map this gene to human chromosome 19 (p13.2-q13.3). Our studies also demonstrate that a subclone from one of the BamHI fragments detects a 3.0 kb transcript in primary and secondary transfectants.

PMID: 1923531 [PubMed - indexed for MEDLINE]  