Analyses of Microsatellite Instability and the Transforming Growth Factor-β Receptor Type II Gene Mutation in Sporadic Human Gastrointestinal Cancer

Tomita, Shuji; Miyazato, Hiroshi; Tamai, Osamu; Muto, Yoshihiro; Toda, Takayoshi

doi:10.1016/s0165-4608(99)00074-6

Cited by 12 publications

(6 citation statements)

References 16 publications

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“…In prior studies of gallbladder cancer, there are only a few reports, with small numbers of cases, using varied numbers and types of microsatellite markers, so that comparisons with other tumor types are difficult. 12,[29][30][31][32] Using the NCI criteria, we analyzed a large series of early and advanced gallbladder cancers for MSI. In addition, we examined pre-malignant glands for the same alterations as those seen in the adjacent tumors, and correlated our results with the immunohistochemical (IHC) expression of the MMR system and the clinicopathological findings.…”

Section: Introductionmentioning

confidence: 99%

Microsatellite instability in preneoplastic and neoplastic lesions of the gallbladder

Roa

Correa

et al. 2005

J Gastroenterol

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Section: Introductionmentioning

confidence: 99%

Microsatellite instability in preneoplastic and neoplastic lesions of the gallbladder

Roa

Correa

et al. 2005

J Gastroenterol

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“…TGFβRII is a protein of the serine-threonine kinase family which mediates TGFβ regulation of cell proliferation and tissue differentiation Lin and Wang 1992). Frameshift mutations in the (A)10 tract of this gene have been reported to be frequent in MSI positive colorectal cancers (Tomita et al 1999), but in our series only three of the ten tumors (TP170, TP171, and TP197) had high error rates of 80%. This observation indicates that in the above three tumors growth advantages resulting from frameshifts in TGFβRII were probably important in neoplastic progression.…”

Section: Discussionmentioning

confidence: 58%

Differential rates of frameshift alterations in four repeat sequences of hereditary nonpolyposis colorectal cancer tumors

et al. 2002

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DNA sequences of mono-, di-, and trinucleotide repeats are prone to replication errors and thus constitute mutational hot spots. This is well illustrated by the occurrence of DNA microsatellite instability in tumors from patients affected by hereditary nonpolyposis colorectal cancer (HNPCC) resulting from a defect in a gene that participates in postreplicative DNA mismatch repair (MMR). We selected repeat sequences present within coding regions of four genes involved in either cell proliferation or promotion of apoptosis. These repeats consisted of (A)10 in the TGF beta RII, (G)8 in the BAX, (A)8 in the CASP1, and (CCA)7 in the APP genes. These repeats were analyzed in ten tumors from HNPCC patients carrying a germline pathogenic mutation in the MMR gene MLH1. For each tumor the rate of somatic replication errors was measured by sequencing 20-50 cloned PCR-amplified fragments. Substantial intertumor variations were observed in the pattern of repeat alterations, with error rates varying between 12% and 80% for TGF beta RII, 2% and 84% for BAX, 0% and 30% for CASP1, and 0% to 18% for APP. The BAX repeat error rate did not exceed 20% in nine of the ten tumors, in contrast to results from previous studies. High error rates in more than one gene in a same tumor suggested additive selective effects from inactivation of different pathways influencing tumorigenesis. Our methodology can contribute to define tumor characteristics and may, if applied to genes strongly involved in tumorigenesis, improve tumor classification and outcome prediction.

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“…Although MSI occurs in a third of esophageal carcinomas, TbR-II frameshift mutations have not been reported (Tomita et al, 1999b;Tanaka et al, 2000).…”

Section: Esophageal Cancermentioning

confidence: 99%

Role of transforming growth factor beta in cancer

2001

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Transforming growth factor beta (TGF-beta) is an effective and ubiquitous mediator of cell growth. The significance of this cytokine in cancer susceptibility, cancer development and progression has become apparent over the past few years. TGF-beta plays various roles in the process of malignant progression. It is a potent inhibitor of normal stromal, hematopoietic, and epithelial cell growth. However, at some point during cancer development the majority of transformed cells become either partly or completely resistant to TGF-beta growth inhibition. There is growing evidence that in the later stages of cancer development TGF-beta is actively secreted by tumor cells and not merely acts as a bystander but rather contributes to cell growth, invasion, and metastasis and decreases host-tumor immune responses. Subtle alteration of TGF-beta signaling may also contribute to the development of cancer. These various effects are tissue and tumor dependent. Identifying and understanding TGF-beta signaling pathway abnormalities in various malignancies is a promising avenue of study that may yield new modalities to both prevent and treat cancer. The nature, prevalence, and significance of TGF-beta signaling pathway alterations in various forms of human cancer as well as potential preventive and therapeutic interventions are discussed in this review.

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Analyses of Microsatellite Instability and the Transforming Growth Factor-β Receptor Type II Gene Mutation in Sporadic Human Gastrointestinal Cancer

Cited by 12 publications

References 16 publications

Microsatellite instability in preneoplastic and neoplastic lesions of the gallbladder

Microsatellite instability in preneoplastic and neoplastic lesions of the gallbladder

Differential rates of frameshift alterations in four repeat sequences of hereditary nonpolyposis colorectal cancer tumors

Role of transforming growth factor beta in cancer

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