Extensive but hemiallelic methylation of the hMLH1 promoter region in early-onset sporadic colon cancers with microsatellite instability

2004 ◽  
Vol 2 (2) ◽  
pp. 147-156 ◽  
Author(s):  
Yasuyuki Miyakura ◽  
Kokichi Sugano ◽  
Takayuki Akasu ◽  
Teruhiko Yoshida ◽  
Masato Maekawa ◽  
...  
Keyword(s):  
Microsatellite Instability ◽  
Early Onset ◽  
Promoter Region ◽  
Colon Cancers

Automated, Multiplex Assay for High-Frequency Microsatellite Instability in Colorectal Cancer

2003 ◽  
Vol 21 (16) ◽  
pp. 3105-3112 ◽  
Author(s):  
G.M. Nash ◽  
M. Gimbel ◽  
J. Shia ◽  
A.T. Culliford ◽  
D.R. Nathanson ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Microsatellite Markers ◽  
High Frequency ◽  
Early Onset ◽  
Cancer Survival ◽  
Multiplex Assay ◽  
Colon Cancers ◽  
Individual Marker ◽  
The Individual

Purpose: In a series of hereditary nonpolyposis colorectal cancer (HNPCC) patients, we evaluated the sensitivities of the individual microsatellites recommended by the National Cancer Institute (NCI) consensus workshop for detection of high-frequency microsatellite instability (MSI-H). On the basis of this evaluation, we developed a three-marker assay that assigns microsatellite instability (MSI) in a multiplex polymerase chain reaction. Methods: Individual marker sensitivity was assessed in 18 HNPCC tumors. Multiplex and NCI assays were then assessed in a series of 120 patients with early-onset colon cancer. Results: The sensitivity of microsatellite markers BAT25, BAT26, D2S123, D5S346, and D17S250 for ASI in HNPCC cancers was 100%, 94%, 72%, 50%, and 50%, respectively. The three most accurate markers were combined and optimized in a multiplex assay that assigned MSI-H whenever at least two of three markers revealed ASI. In early-onset colon cancers, the prevalence of MSI-H determined by the multiplex assay and by the NCI assay was 16% and 23%, respectively. The additional MSI-H tumors and patients with MSI-H identified by the NCI assay lacked the traits characteristic of MSI-H seen in tumors and patients identified by the multiplex assay: retention of heterozygosity (NCI additional 22% v multiplex 84%; P = .003), characteristic tumor morphology (0% v 64%; P = .006), and 5-year cancer survival rate (44% v 100%; P = .0003). Conclusion: The multiplex assay identifies colon cancers with MSI-H by assessing three highly accurate microsatellite markers. This assay identifies a smaller MSI-H cohort with more homogeneous clinical features and is superior as a marker of favorable prognosis. It merits prospective evaluation as a marker of prognosis and as a screening test for HNPCC.

Microsatellite Instability as a Predictor of Outcomes in Colorectal Cancer in the Era of Immune-Checkpoint Inhibitors

2021 ◽  
Vol 22 ◽  
Author(s):  
Csongor György Lengyel
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Immune Checkpoint ◽  
Predictive Value ◽  
Checkpoint Inhibitors ◽  
Tumor Infiltrating Lymphocytes ◽  
Primary Objective ◽  
Dna Mismatch ◽  
Dominant Component ◽  
Colon Cancers

: The microsatellite instable phenotype resulting from errors in DNA mismatch repair proteins accounts for as far as 15 to 20% of non-hereditary colon cancers but is scarce in rectal cancer. It has been shown that the increased existence of tumor-specific neoantigens in hypermutated tumors is correlated with higher tumor-infiltrating lymphocytes (TILs) and overexpression of immune checkpoint receptors and ligands, mainly PD-1 and PD-L1. In particular, the data gained up to now gives evidence that neoantigen recognition constitutes a dominant component in the course of immunotherapies. This review's primary objective is to describe current approvals and summarize present knowledge about the outcomes of immuno-oncology treatment of microsatellite instable colorectal cancer (CRC). The secondary objective is to give a narrative report about testing methodologies, prognostics, and the predictive value of microsatellite instability. For this purpose, a literature review was performed, focusing on published clinical trial results, ongoing clinical trials and timelines, testing methods, and prognostic and predictive value of MSI. Following four recent FDA approvals of immunotherapy of MSI-high CRC, further work should be warranted by pathology societies towards standardization and rising concordance and reproducibility across the IHC/MSI testing landscape in order to facilitate professionals to offer better survival options for patients with CRC.

Increased risk for abnormalities on perioperative colon screening in patients with microsatellite instability–positive endometrial carcinoma

2006 ◽  
Vol 16 (6) ◽  
pp. 1980-1986 ◽  
Author(s):  
B. M. Buttin ◽  
M. A. Powell ◽  
P. J. Goodfellow ◽  
S. N. Lewin ◽  
R. K. Gibb ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Microsatellite Instability ◽  
Medical Records ◽  
Fisher Exact Test ◽  
Exact Test ◽  
Molecular Stratification ◽  
Colon Cancers ◽  
Increased Risk ◽  
Primary Colon ◽  
Endometrial Cancers

Microsatellite instability (MSI) is a feature of certain hereditary and sporadic endometrial and colon cancers. We set out to determine whether molecular stratification of endometrial cancers based on tumor MSI status could help identify patients at increased risk for abnormalities found on perioperative colon screening. From a prospectively accrued series of 413 patients, medical records were reviewed from 94 patients with MSI positive (MSI+) and 94 patients with MSI negative (MSI−) endometrial cancers, matched by year of diagnosis. We reviewed clinicopathologic data and results of perioperative colon screening. Differences were analyzed using Fisher exact test and logistic regression analysis. There were no significant clinicopathologic differences between the two cohorts. Sixty-five percent of patients in each group underwent perioperative colon screening. However, patients with MSI+ cancers had a twofold increase in the frequency of colonic abnormalities (30% versus 14.8%, P= 0.044) over those with MSI− cancers. Furthermore, the only primary colon cancers (N= 2) were found in women with MSI+ endometrial cancers that were unmethylated at the MLH1 promoter. Our data suggest that patients with MSI+ endometrial cancers are at increased risk for abnormalities on perioperative colon screening. Those with MSI+MLH1 unmethylated cancers appear to be at highest risk.

scholarly journals Microsatellite instability in early onset and familial colorectal cancer.

1996 ◽  
Vol 33 (12) ◽  
pp. 981-985 ◽  
Author(s):  
C Brassett ◽  
J A Joyce ◽  
N J Froggatt ◽  
G Williams ◽  
D Furniss ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Early Onset ◽  
Familial Colorectal Cancer

scholarly journals MUC Gene Abnormalities in Sporadic and Hereditary Mucinous Colon Cancers with Microsatellite Instability

2005 ◽  
Vol 21 (3) ◽  
pp. 121-126 ◽  
Author(s):  
Chiara Pastrello ◽  
Manuela Santarosa ◽  
Mara Fornasarig ◽  
Roberto Sigon ◽  
Tiziana Perin ◽  
...  
Keyword(s):  
Microsatellite Instability ◽  
Southern Blotting ◽  
Repetitive Sequences ◽  
Variable Number ◽  
Molecular Pathway ◽  
Colon Cancers ◽  
Tandem Repetition ◽  
Indirect Consequence ◽  
Muc Genes ◽  
Gene Alterations

Aim of this study was verifying whether mucin producing colon cancers (CRCs) could develop through a molecular pathway involving microsatellite instability (MSI) and MUC gene alterations. Out of 49 CRCs expressing variable amounts of mucin, 22 (44.9%) were MSI-H and 5 (10.2%) were MSI-L. MUC genes were analyzed by Southern blotting and extra bands were evident in the Variable Number Tandem Repetition (VNTR) regions of MUC2 (5 cases) and MUC5AC (2 cases), but not MUC1 and MUC4 genes. Since the somatic VNTR abnormalities were detected in 6 MSI-H and in 1 MSI-L tumors, they seem to be peculiar of mismatch repair defective CRCs. Our finding suggests that alteration and/or loss of structurally normal MUC genes may be an important step in the neoplastic molecular pathway of a subset of CRCs and that mutations involving VNTR repetitive sequences may exist in MSI tumors as a direct and/or indirect consequence of an inefficient MMR system.

Sign in / Sign up

Export Citation Format

Share Document