Diagnostic value of DNA alteration: loss of heterozygosity or allelic imbalance—promising for molecular staging of prostate cancers

Abstract

The biological behavior of prostate cancer is uncertain, and therefore, search for molecular prognostic markers associated with disease progression seems to be essential. We performed microsatellite allelotyping of DNA isolated from primary prostate tumors biopsies (prostate adenocarcinoma, PCa). We evaluated the frequency of allelic imbalance (AI), including loss of heterozygosity and/or microsatellite imbalance (LOH/MSI) as well as the association of these DNA alterations with clinicopathological variables. We assessed the significance of LOH/MSI alterations in selected imprinted and non-imprinted chromosomal regions (IR and NIR) in PCa. A total of 50 biopsies of prostate tumor (containing >75 % tumor cells) were histologically examined confirming prostate carcinoma. Microsatellite allelotyping using 16 microsatellite markers linked to the following chromosomal regions: 1p31.2, 3p21.3–25.3, 7q32.2, 9p21.3, 11p15.5, 12q23.2, and 16q22.1 was performed. The incidence of LOH/MSI alterations in prostate tumor cells was the highest for chromosomal regions 7q32.2 and 16q22.1 (31.25 and 26.60 %, respectively), followed by 1p31.2 and 3p21.3–25.3 (26.50 and 17.40 %, respectively). Statistically significant increase in LOH/MSI alterations has been observed for markers: D1S2137 (1p region; p = 0.00032), D9S974 (9p region; p = 0.0017), and D16S3025 (16q region; p = 0.0017). Statistically significant differences in frequency of LOH/MSI alterations in particular chromosomal regions have been found for 1p31.2, 7q32.2 and 16q22.1 (p = 0.027, p = 0.012 and p = 0.031, respectively). We documented statistically significant association between Fractional Allele Loss (FAL) index and advanced tumor stage (p < 0.05). We suggest that genomic instability of LOH/MSI type is a frequent event in prostate carcinogenesis and assessed as FAL index has clinical value for the molecular staging of prostate cancer in (TRUS)-guided prostate biopsy material.

Effects of long-term aspirin use on molecular alterations in precancerous gastric mucosa in patients with and without gastric cancer

“…In cases that were indistinguishable between MSI and loss of heterozygosity 54 , the allelic imbalance (AI) ratio was calculated. MSI was determined to be positive when the AI ratio (normal allele 1:normal allele 2/tumor allele 1:tumor allele 2) was <0.67 or >1.35, as previously reported 40 , 53 (Supplementary Fig. S2 ).…”

“…4.0 (Applied Biosystems). The MSI status was judged according to previous reports 40 , 53 , 54 (Supplementary Fig. S2 ).…”

CMTM4 is frequently downregulated and functions as a tumour suppressor in clear cell renal cell carcinoma

“…CMTM4 is tightly linked with CMTM1-3 on chromosome 16q22.1, a genomic region prone to both genetic and epigenetic modifications in various cancers. Chromosomal aberrations, such as deletions, amplifications [ 26 – 29 ], single nucleotide polymorphisms (SNPs) [ 30 ], loss of heterozygosity (LOH) and microsatellite instability (MSI) [ 31 , 32 ], as well as aberrant methylations [ 29 ], occur frequently in this region in different types of malignancies. Our previous studies have also shown that CMTM3 is frequently inactivated by promoter CpG methylation [ 18 ].…”

Long-term effects of H. pylori eradication on epigenetic alterations related to gastric carcinogenesis

“…As previously reported 22 , 25 , 43 , 49 , the following five microsatellite loci on chromosomes were examined for MSI based on the revised Bethesda panel 48 – 50 : BAT26, BAT25, D2S123, D5S346, and D17S250. MSI status was judged according to previous reports 43 , 49 , 51 , 52 (Supplementary Fig. S5 ).…”