Oncogene Mutation (oncogene + mutation)

Distribution by Scientific Domains


Selected Abstracts


Diagnostic usefulness of laparoscopic fine-needle aspiration for intraductal papillary tumor of the pancreas

DIGESTIVE ENDOSCOPY, Issue 4 2001
Tomonori Akagi
A 67-year-old man who was followed up for 20 years for a diagnosis of chronic pancreatitis developed a unilocular cystic lesion in the pancreatic body and a gallstone. The cystic lesion (3.0 cm in diameter) was considered to be a pseudocyst with suspicion of a mucinous cystic tumor. Laparoscopic ultrasonography and fine-needle aspiration (FNA) were performed following laparoscopic cholecystectomy. Under laparoscopic observation, the pinhole puncture was immediately closed. Analysis of the fluid revealed clusters of epithelial cells with mild atypia, remarkably elevated tumor markers (carcinoembryonic antigen and CA19-9) and a K- ras oncogene mutation. Distal pancreatectomy was performed 3 months after laparoscopic FNA and the pancreatic mass was diagnosed as an intraductal papillary tumor. The patient's postoperative course was uneventful and he continues to do well without signs of recurrence. Laparoscopic FNA appears useful and safe for the diagnosis of cystic masses in the pancreas. [source]


Bone morphogenic protein 3 inactivation is an early and frequent event in colorectal cancer development

GENES, CHROMOSOMES AND CANCER, Issue 6 2008
Kim Loh
Bone morphogenic proteins (BMPs) are members of the TGFB growth factor superfamily with well-described functions in bone formation. Although disrupted BMP signalling in tumor development has more recently been investigated, a role for BMP3 in colorectal cancer (CRC) has remained largely unexplored. The aim of this study was to investigate BMP3 disruption in CRCs in relation to both the traditional and serrated pathways of tumor progression. BMP3 was down-regulated as assessed by real-time PCR in 50 of 56 primary tumors (89%). Bisulfite sequencing of the putative promoter revealed extensive hypermethylation in the cell line HT29, in which expression could be restored by treatment with a methyltransferase inhibitor. Aberrant hypermethylation was observed in 33/60 (55%) tumors and was highly correlated with microsatellite instability (P < 0.01), the CpG Island Methylator Phenotype (P < 0.01), BRAF oncogene mutation (P < 0.01), and proximal location (P < 0.001). Methylation was also frequently observed in serrated and traditional adenomatous polyps (22/29, 76%). Re-introduction of BMP3 into cell lines revealed marked growth suppression supporting the functional relevance of this alteration in colorectal tumor development. This study provides molecular and functional data supporting the importance of BMP3 silencing as an early and frequent event in colorectal tumors progressing via the serrated and traditional pathways. © 2008 Wiley-Liss, Inc. [source]


Levels of 4-aminobiphenyl-induced somatic H- ras mutation in mouse liver DNA correlate with potential for liver tumor development,

MOLECULAR CARCINOGENESIS, Issue 4 2005
Barbara L. Parsons
Abstract The utility of liver H- ras codon 61 CAA to AAA mutant fraction as a biomarker of liver tumor development was investigated using neonatal male mice treated with 4-aminobiphenyl (4-ABP). Treatment with 0.1, 0.3, or 1.0 ,mol 4-ABP produced dose-dependent increases in liver DNA adducts in B6C3F1 and C57BL/6N mice. Eight months after treatment with 0.3 ,mol 4-ABP or the DMSO vehicle, H- ras codon 61 CAA to AAA mutant fraction was measured in liver DNA samples (n,=,12) by allele-specific competitive blocker-polymerase chain reaction (ACB-PCR). A significant increase in average mutant fraction was found in DNA of 4-ABP-treated mice, with an increase from 1.3,×,10,5 (control) to 44.9,×,10,5 (treated) in B6C3F1 mice and from 1.4,×,10,5 to 7.0,×,10,5 in C57BL/6N mice. Compared with C57BL/6N mutant fractions, B6C3F1 mutant fractions were more variable and included some particularly high mutant fractions, consistent with the more rapid development of liver foci expected in B6C3F1 mouse liver. Twelve months after treatment, liver tumors developed in 79.2% of 4-ABP-treated and 22.2% of control B6C3F1 mice; thus measurement of H- ras mutant fraction correlated with subsequent tumor development. This study demonstrates that ACB-PCR can directly measure background levels of somatic oncogene mutation and detect a carcinogen-induced increase in such mutation. Published 2005 Wiley-Liss, Inc. [source]


Genetic and epigenetic alterations in the differential diagnosis of malignant melanoma and spitzoid lesion

BRITISH JOURNAL OF DERMATOLOGY, Issue 6 2007
M. Takata
Summary Background, The histopathological differentiation of malignant melanoma and Spitz naevus often presents diagnostic problems. Objectives, We aimed to find out applicable diagnostic parameters other than routine pathology. Methods, The cases included conventional melanomas and Spitz naevi as well as atypical spitzoid lesions that had posed diagnostic difficulties. We examined hotspots of mutation in the BRAF, NRAS and HRAS genes by polymerase chain reaction-based direct sequencing. We also analysed DNA copy number aberrations and the methylation of CpG sequences in several cancer-related genes by utilizing a novel methylation-specific multiplex ligation-dependent probe amplification method. Results, Twenty three of 24 conventional melanomas showed at least one of the genetic and epigenetic alterations examined, although one acral melanoma did not show any alteration. By sharp contrast, 12 Spitz naevi with an unambiguous histopathology showed no or few chromosomal aberrations, no oncogene mutations and no methylation of CpG sequences. Of the 16 ambiguous spitzoid lesions, most of which were designated atypical Spitz tumour by one of the authors, all but one showed no mutations, no methylations and few copy number aberrations. However, three tumours showed copy number loss of the cyclin-dependent kinase inhibitor 2A gene (CDKN2A), an alteration observed frequently in melanomas but not found in conventional Spitz naevi. These results show that, although most atypical Spitz tumours do not differ from conventional Spitz naevi showing virtually no genetic and epigenetic aberrations, some cases may have chromosomal aberrations that include copy number loss of the CDKN2A gene. Conclusions, Genetic and epigenetic analyses may be useful as an additional diagnostic tool to distinguish between melanoma and Spitz naevus, and may help to define subgroups in atypical Spitz tumours. [source]