Microsatellite instability and loss of heterozygosity detected in middle-aged patients with sporadic colon cancer: A retrospective study

Kamat, Nasir; Khidhir, Mohammed A.; Alashari, Mouied; Rannug, Ulf

doi:10.3892/ol.2013.1573

Cited by 10 publications

(8 citation statements)

References 36 publications

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“…3). This rate turned out to be lower as compared with frequency of MSI, which was determined by other researchers that probably is associated with different prevalence of MSI in different ethnic groups [28]. For instance, according to the literature, MSI is detected in 25-30% of all endometrial carcinomas [25].…”

Section: Resultsmentioning

confidence: 78%

The Study of Mismatch Repair in Endometrial Cancer Patients With a Family History of Cancer

Lg¹,

Brieieva²,

Ka³

et al. 2015

Exp. Onc.

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Aim: To assess the expression of mismatch repair (MMR) proteins MSH2 and MLH1 and carry out microsatellite analysis in patients with endometrial cancer (EC) with regard to the family history of cancer. Materials and Methods: Morphological and immunohistochemical study was performed on tumor tissue samples of 49 EC patients. Microsatellite instability was determined using PCR with primers which flank microsatellite region BAT-26. Results: A tendency to a decreased expression of both MSH2 and MLH1 markers in a group of EC patients with a family history of cancer as compared with a group without aggregation of cancer in family history was observed (labeling index — LI — was 36.1 ± 8.1% and LI 20.7 ± 9.1% versus LI 48.0 ± 5.8% and 33.8 ± 5.8%, respectively). It was determined that the number of EC patients with tumors deficient by expression of MMR markers was reliably higher in a group of patients with a family history of cancer than in a group of patients without aggregation of cancer in fami ly history (р < 0.05). It was shown that in a group of EC patients with a family history of cancer, MMR-proficient tumors were detected in 38.5% of cases. Microsatellite instability was determined in 10.7% of EC patients including one patient with aggregation of Lynch-associated tumors in family history. Conclusion: Family history of cancer of EC patients is associated with malfunctioning of the MMR system as well as may be related to alternative molecular mechanisms.

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Section: Resultsmentioning

confidence: 78%

The Study of Mismatch Repair in Endometrial Cancer Patients With a Family History of Cancer

Lg¹,

Brieieva²,

Ka³

et al. 2015

Exp. Onc.

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“…Meanwhile, the presence of LOH in the primary tumour may also be predictive of lymph node metastasis [31] and poor prognosis [32] . Previous studies have revealed a significant association between LOH and cancer stage [33] ; however, the study by Szukala et al did not reveal the predictive value of LOH with respect to local relapse in patients with laryngeal carcinoma [25] . We demonstrate herein that LOH in patients with laryngeal carcinoma is associated with a poor prognosis.…”

Section: Discussionmentioning

confidence: 84%

LOH Detected by Microsatellite Markers Reveals the Clonal Origin of Recurrent Laryngeal Squamous Cell Carcinoma

2014

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BackgroundThe question of whether “recurrent” laryngeal carcinoma is truly a new tumour with a clonal origin that differs from that of the primary tumour has remained unanswered. The objective of this study was to determine whether recurrent tumours have the same genetic basis as primary tumours, as the answer to this question is important for the development of treatment strategies.Materials and MethodsMatched samples consisting of primary tumour, recurrent tumour and normal tissue were obtained from the same patient. A total of 37 patients with laryngeal cancer were examined for loss of heterozygosity (LOH) on the 3p, 5p, 7q, 8p, 9p, 13p, 17p and 18q chromosomal arms using PCR to amplify microsatellite markers. All patients were routinely followed up and 5-year survival rates were calculated using directly calculating method and Kaplan-Meier's method.ResultsA total of 28 out of 37 (75.6%) patients showed LOH at a minimum of one locus, and 19 out of 37 (51.3%) patients showed LOH at two loci. Primary and recurrent tumours in each patient showed identical allelic loss patterns and incidence rates. Patients without LOH had a longer average time to recurrence than patients with LOH (P<0.05). Additionally, patients with LOH had a longer average smoking duration prior to surgery than patients without LOH (P<0.05). The 5-year survival rates were 32.14%in patients with LOH versus 44.4% in patients without LOH.ConclusionsThe data indicate that primary and recurrent tumours have the same clonal origin. This result implies that we failed to radically resect the primary tumours and/or micrometastases in these patients. Consequently, some form of adjunctive therapy may be necessary. Additionally, the data indicate that the recurrence of laryngeal squamous cell carcinoma is closely related to chromosomal aberrations (specifically LOH).

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“…Other studies performed on LOH/MSI in head and neck cancers, colon cancer, ovarian cancer, and in cervical cancer in different populations with unknown HIV-1 status, reported frequent LOH/MSI in many chromosomes, with LOH/MSI frequencies that varied from 17 to 90% (9, 17, 18, 21, 30, 51). However, in this study, the LOH/MSI frequencies vary from 13 to 79% (Table 5).…”

Section: Discussionmentioning

confidence: 94%

“…MSI is a locus-specific change in the length of a short tandem repeat of nucleotide sequence in tumor genomic DNA when compared to the length in the normal genomic DNA (e.g., derived from white blood cells) from the same patient (18). MSI is caused by mutational inactivation of genes involved in DNA damage-repair (19).…”

Section: Introductionmentioning

confidence: 99%

Investigation of Cervical Tumor Biopsies for Chromosomal Loss of Heterozygosity (LOH) and Microsatellite Instability (MSI) at the HLA II Locus in HIV-1/HPV Co-infected Women

et al. 2019

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Background: A subgroup of women who are co-infected with human immunodeficiency virus type 1 (HIV-1) and human papillomavirus (HPV) progress rapidly to cervical disease regardless of high CD4 counts. Chromosomal loss of heterozygosity (LOH) and microsatellite instability (MSI) are early frequent genetic alterations occurring in solid tumors. Loss of an allele or part of a chromosome can have multiple functional effects on immune response genes, oncogenes, DNA damage-repair genes, and tumor-suppressor genes. To characterize the genetic alterations that may influence rapid tumor progression in some HIV-1-positive women, the extent of LOH and MSI at the HLA II locus on chromosome 6p in cervical tumor biopsy DNA samples with regard to HIV-1/HPV co-infection in South African women was investigated.Methods: A total of 164 women with cervical disease were recruited for this study, of which 74 were HIV-1-positive and 90 were HIV-1-seronegative. DNA from cervical tumors and matched buccal swabs were used for analyses. Six fluorescently-labeled oligonucleotide primer pairs in a multiplex PCR amplification were used to study LOH and MSI. Pearson chi-squared test for homogeneity of proportions using an exact p value, a two-proportion Z-score test, ROC curves and a logistic regression model were used for statistical analyses. All p-values were corrected for false discovery rate (FDR) using the Benjamini-Hochberg test and the adjusted p-values (q-values) were reported. All tests were significant when both p and q < 0.05.Results: Tumor DNA from HIV-1/HPV co-infected women demonstrated a higher frequency of LOH/MSI at the HLA II locus on chromosome 6p21.21 than tumor DNA from HIV-1-seronegative women (D6S2447, 74.2 vs. 42.6%; p = 0.001, q = 0.003), D6S2881 at 6p21.31 (78.3 vs. 42.9%; p = 0.002, q = 0.004), D6S2666 at 6p21.32 (79 vs. 57.1%; p = 0.035, q = 0.052), and D6S2746, at 6p21.33 (64.3 vs. 29.4%; p < 0.001, q < 0.001), respectively.Conclusions: HPV infection alone can induce LOH/MSI at the HLA II locus in cervical tumor DNA, whereas HIV-1 co-infection exacerbates it, suggesting that this may accelerate cervical disease progression in a subgroup of HIV-1-positive women.

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Microsatellite instability and loss of heterozygosity detected in middle-aged patients with sporadic colon cancer: A retrospective study

Cited by 10 publications

References 36 publications

The Study of Mismatch Repair in Endometrial Cancer Patients With a Family History of Cancer

The Study of Mismatch Repair in Endometrial Cancer Patients With a Family History of Cancer

LOH Detected by Microsatellite Markers Reveals the Clonal Origin of Recurrent Laryngeal Squamous Cell Carcinoma

Investigation of Cervical Tumor Biopsies for Chromosomal Loss of Heterozygosity (LOH) and Microsatellite Instability (MSI) at the HLA II Locus in HIV-1/HPV Co-infected Women

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