The clinical importance and prognostic implications of microsatellite instability in sporadic cancer

Lawes, D; SenGupta, Sioban; Boulos, P B

doi:10.1053/ejso.2002.1399

Cited by 114 publications

(98 citation statements)

References 134 publications

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“…2 Some studies showed that MSI positivity in pathologically negative surgical margins of HNSCC can independently predict local recurrence. 67,68 Some authors found no correlation between MSI in HNSCC and survival, 6 whereas others describe a better prognosis for MSI-positive patients, 69 as recently also published for colorectal cancer.…”

Section: Methodological Issuesmentioning

confidence: 99%

“…1 MSI is also typically associated with Turcot's and Muir -Torre syndrome. 2 However, the frequency and clinical value of MSI in other solid tumors including HNSCC differs widely, largely due to an obvious variance in used methods and criteria. 2 Concerning LOH, different techniques have been developed to assess this type of alterations.…”

Section: Introductionmentioning

confidence: 99%

“…2 However, the frequency and clinical value of MSI in other solid tumors including HNSCC differs widely, largely due to an obvious variance in used methods and criteria. 2 Concerning LOH, different techniques have been developed to assess this type of alterations. The further report on LOH in this work will only refer to LOH detected with microsatellite markers.…”

Section: Introductionmentioning

confidence: 99%

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The clinical relevance of microsatellite alterations in head and neck squamous cell carcinoma: a critical review

Schutter¹,

Spaepen²,

Bride

et al. 2007

Eur J Hum Genet

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Triggered by the existing confusion in the field, the current paper aimed to review the current knowledge of both microsatellite instability (MSI) and loss of heterozygosity (LOH) detected by microsatellite markers in head and neck squamous cell carcinoma (HNSCC), and to provide the reader with an assessment of their prognostic and predictive value in this tumor type. For both MSI and LOH, various detection methods were included such as mono-and polynucleotidemarkers and gel-as well as automated analyses. Only studies based on PCR techniques with microsatellite markers were considered. Taking the methodological problems occurring in investigations with microsatellite markers into account, LOH seems to be more common than MSI in HNSCC. Although both types of microsatellite alterations have been correlated with clinicopathological features of this tumor type, only LOH seems to have a clear prognostic value. The predictive value of both MSI and LOH is debatable. More research has to be performed to clearly establish LOH detection as a translational application in the HNSCC field, aiming to predict response to treatments or outcome, and eventually to use as a therapeutic target.

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Section: Methodological Issuesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The clinical relevance of microsatellite alterations in head and neck squamous cell carcinoma: a critical review

Schutter¹,

Spaepen²,

Bride

et al. 2007

Eur J Hum Genet

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“…1 MIN has been demonstrated in over 90% of hereditary non-polyposis colorectal cancers and in 10-15% of both sporadic colorectal and ovarian cancers. [2][3][4] MIN cancers are characterized by a defect in the mismatch repair (MMR) system, which would normally identify and excise DNA replication errors, such as base/base mismatches and insertion/deletion loops (IDLs). IDLs are caused by slippage of the DNA polymerase during the replication of microsatellite sequences, causing insertions or deletions in repetitive DNA sequences in the genome and can therefore lead to widespread genomic instability.…”

Section: Introductionmentioning

confidence: 99%

“…[8][9][10][11] Of greater clinical concern is the observation that cancer cells can gain a MIN phenotype and acquire resistance to such chemotherapeutics. 3 As of 2003, the Food and Drug Administration (FDA) has not designated any gene therapy approach for cancer as safe and effective. Attractive gene therapy targets tend to focus on introducing tumor suppressors or inactivating oncogenes for the purpose of slowing or stopping tumor growth.…”

Section: Introductionmentioning

confidence: 99%

Persistent mismatch repair deficiency following targeted correction of hMLH1

et al. 2006

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The use of gene therapy to correct mutated or lost gene function for the treatment of human cancers has been an active, yet problematic area of biomedical research. Many technical difficulties, including efficient tissue-specific delivery, integration site specificity and general toxicity, are being addressed. Little is known, however, about the genetic and phenotypic stability that accompanies a successful gene-specific targeting event in a cancer cell. This question was addressed following the creation of a colon cancer cell line in which a mutated hMLH1 gene was corrected via targeted homologous recombination. This correction resulted in the expression of wild-type hMLH1 protein, restoration of the hPMS2 protein and mismatch repair (MMR) proficiency. One of two hMLH1-corrected clones, however, was found to retain defects in MMR activity. These cells continued to express the corrected hMLH1 protein, but had lost expression of another MMR protein, hMSH6. DNA sequence analysis of the hMSH6 gene revealed biallelic expansions of a cytosine repeat region in exon 5 that result in frameshifts leading to premature stop codons. These findings suggest that, similar to acquired drug resistance, the presence of genetically heterogeneous cancer cell populations or acquisition of compensatory mutations can result in 'resistance' to gene replacement therapy.

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Colorectal Cancer

2006

Wiley Handbook of Current and Emerging Drug Therapies

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The clinical importance and prognostic implications of microsatellite instability in sporadic cancer

Cited by 114 publications

References 134 publications

The clinical relevance of microsatellite alterations in head and neck squamous cell carcinoma: a critical review

The clinical relevance of microsatellite alterations in head and neck squamous cell carcinoma: a critical review

Persistent mismatch repair deficiency following targeted correction of hMLH1

Colorectal Cancer

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