“Low-risk” and “High-risk” HPV-infection and K-ras Gene Point Mutations in Human Cervical CancerA Study of 31 Cases

STENZEL, A; Semczuk, Andrzej; Rozynska, K; Ja, Jakowicki; Wojcierowski, Jacek

doi:10.1016/s0344-0338(04)70133-8

Cited by 11 publications

(6 citation statements)

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“…All mutated cases were HPV 16 positive and presented poorly or moderately differentiated squamous carcinomas (Table V). The results are in line with other publications which suggest that ras activations are present in less differentiated carcinomas [Tenti et al, 1995;Stenzel et al, 2001] and associated to worse prognosis [Soh et al, 2002].…”

Section: Discussionsupporting

confidence: 93%

Human papillomavirus and mutated H‐ras oncogene in cervical carcinomas and pathological negative pelvic lymph nodes: A retrospective follow‐up

Landro

Dalbert

Picconi

et al. 2008

Journal of Medical Virology

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The metastasis status of pelvic lymph nodes (PLNs) seems to be a predictive factor of survival. It was suggested that the presence of HPV DNA and other biological markers in PLN may indicate a sub clinical early metastasis. The aim was to describe the prevalence and distribution patterns of HPV DNA and H-ras mutations in intra operatively obtained cervical tumors and PLN. Thirty-seven cervical tumors and 61 lymph node biopsies from 37 patients with cervical cancer were selected. HPV typing and location were performed by PCR/dot blot and in situ hybridization (ISH) respectively. PCR/RFLP was used to scan for mutations in H-ras. Hundred percent of the cervical cancers and 85% of the PLN were HPV positive; co-infection with more than one type was 27%. HPV 16 was detected alone or co-infecting with other types in 84% of tumors and 46% of PLN; the second most frequent viral type was HPV 18 (tumor: 27%; PLN: 20%). In PLN, HPV was located in nuclei or/and cytoplasm of lymphocytes, macrophages, endothelial, and /or stromal cells. H-ras mutations were identified in 5/24 (21%) of patients with cervical tumors showing poor or moderated differentiation. HPV DNA in histological tumor-free PLN not necessary indicate metastasis, but it may be associated to an active immune reaction. Mutated H-ras is probably involved in cervical carcinogenesis and its detection in tumor and metastasis free PLN may be related to early metastasis or recurrence in at least a subset of poorly differentiated cervical tumors.

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Section: Discussionsupporting

confidence: 93%

Human papillomavirus and mutated H‐ras oncogene in cervical carcinomas and pathological negative pelvic lymph nodes: A retrospective follow‐up

Landro

Dalbert

Picconi

et al. 2008

Journal of Medical Virology

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“…Activated KRAS is not a factor in vulvar SCC pathogenesis Although activating mutations in KRAS genes are common in cancers (Ellis and Clark, 2000), can be found frequently in one mouse model of SCC (Rehman et al, 2000) and are present in some human SCC and its precursors (Spencer et al, 1995;Stenzel et al, 2001), the present data suggest that KRAS codon 12 mutations are not an early, rate-limiting step in the development of vulvar SCC, a finding in line with Tate et al's (1994) study of vulvar SCC that did not detect activating RAS mutations. However, the nearly 50% frequency of activating KRAS mutations in AN suggest that its presence may be a sign of genomic instability signifying a risk for or necessary step in the acquisition of other mutations, that is TP53 mutations (Knauf et al, 2006).…”

Section: Stem Cells and Epusmentioning

confidence: 99%

Single Base Instability Is Promoted in Vulvar Lichen Sclerosus

Tapp

Feng

Jones

et al. 2007

Journal of Investigative Dermatology

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Single base substitution mutations in codons 248 and 273 of TP53 and codon 12 Kirsten-ras (KRAS) are commonly found in human carcinomas. To determine whether these mutations also occur in normal and inflamed tissues from which carcinomas arise, we utilized the ultra-sensitive polymerase chain reaction/restriction endonuclease/ligase chain reaction mutation assay. Ninety samples of genital skin, including lichen sclerosus (LS) affected skin, adjacent normal and non-adjacent normal, were assayed. Mutations were detected in 103 of 349 assays and consisted of KRAS G34A, G34T, G35A, and TP53 C742T, G818C, C817T, and G818A mutations. Mutant prevalence varied from 1 to 20 per 10(6) wild-type cells. Mutations occurred significantly more frequently in LS (78/224 (35%)) than adjacent normal (20/88 (23%)) and non-adjacent normal genital skin (5/38 (13%)). KRAS G34A mutation was relatively common to all classes of specimen, whereas TP53 gene C742T and G818C mutations were significantly more frequent in LS than normal genital skin. In matched samples, immunohistochemistry evaluation of p53 protein expression revealed the presence of epidermal p53 clones in LS whose presence and number significantly correlated with the presence of TP53 C742T and G818C mutations. Based on these results, it appears oncogenic point mutations occur in normal genital skin, and are selected for in LS.

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“…ONCOLOGY REPORTS 16: 1245REPORTS 16: -1252REPORTS 16: , 2006 Molecular mechanisms underlying the tumorigenesis of colorectal adenomas: Correlation to activated K-ras oncogene of colorectal cancers (9), and 48% of lung cancer (10). Some studies have proposed that K-ras mutations play a significant role in the onset and progression of colorectal cancer (11). Some others have even pointed out the presence of K-ras mutations in ~70% of colorectal cancer and 40% of colonic adenoma >1.0 cm in diameter (12).…”

Section: Introductionmentioning

confidence: 99%

Molecular mechanisms underlying the tumorigenesis of colorectal adenomas: Correlation to activated K-ras oncogene

Wang

Wang²,

Jao³

et al. 2006

Oncol Rep

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Mutations of K-ras gene have been demonstrated in 40-50% of colorectal cancer and large adenoma (>1 cm). This study was intended to clarify the correlation between the existence of K-ras oncogene and the pathological features of colorectal adenomas using our recently developed membrane arrays. Moreover, the downstream genes regulated by K-ras oncogene were explored to serve as potential biomarkers in the early diagnosis and risk assessment of patients with colorectal adenoma. Specimens were collected from 70 patients with colorectal adenoma. The alterations of K-ras oncogene were analyzed by direct sequencing and our constructed membrane arrays, respectively. The results of direct sequencing showed that 21 of 70 samples (30%) had K-ras gene mutations. The most frequently mutated sites included codons 12, 13, 15 and 18. Furthermore, activated K-ras oncogene was identified in 18 of 70 (25.7%) adenoma by membrane arrays. Statistical analyses showed that the membrane array had the accuracy of 90.0%, sensitivity of 88.9%, and specificity of 90.4%. The frequency of the mutational sites of K-ras gene was located as follows: codon 12, 100% (4/4); codon 13, 100% (4/4); codon 15, 75% (6/8); and codon 18, 100% (2/2). The analysis of the correlation between the experimental data and pathological characteristics of adenoma showed that activated K-ras oncogenes were significantly associated with the size, number and histology of adenomas (all P<0.001). Finally, we found the downstream genes activated by K-ras oncogene, including B-cell CLL/ lymphoma 2 (BCL2), Homo sapiens H2A histone family, member Z (H2AFZ), Homo sapiens RAP1B, member of RAS oncogene family (RAP1B), Homo sapiens T-box 19 (TBX19), Homo sapiens E2F transcription factor 4, p107/p130-binding (E2F4) and matrix metallopeptidase 1 (MMP1), of which were overexpressed in most of all examined adenomas. These genes were then suggested to have functions involved in cell growth. The preliminary results indicated that the accuracy of membrane arrays was comparable to conventional DNA sequencing in the detection of activated K-ras oncogenes. Therefore, we propose that activated K-ras oncogene in colorectal adenomas may play an important role in the subsequent colorectal carcinogenesis through a group of K-rasrelated molecular targets.

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“Low-risk” and “High-risk” HPV-infection and K-ras Gene Point Mutations in Human Cervical CancerA Study of 31 Cases

Cited by 11 publications

References 0 publications

Human papillomavirus and mutated H‐ras oncogene in cervical carcinomas and pathological negative pelvic lymph nodes: A retrospective follow‐up

Human papillomavirus and mutated H‐ras oncogene in cervical carcinomas and pathological negative pelvic lymph nodes: A retrospective follow‐up

Single Base Instability Is Promoted in Vulvar Lichen Sclerosus

Molecular mechanisms underlying the tumorigenesis of colorectal adenomas: Correlation to activated K-ras oncogene

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