Loss of heterozygosity (LOH)--implications for human genetic identification.

Abstract

Abstract:The aim of this study was assessment of possible effects of loss of heterozygosity on human genetic identification of histolopathogical tissue sections. DNA templates were extracted from tumour tissue specimens excised from oncological patients and from reference blood samples. AmpFlSTR Identifiler PCR Amplification Kit and ABI 310 Genetic Analyzer (Applera) were used to obtain genetic profiles. Frequency of LOH was calculated for respective samples. Fisher's exact test was performed for statistical analysis. Forty-two percent of the 101 cancer cases analysed were found to possess alterations of the microsatellites manifesting with allelic loss. The most frequently altered loci were D3S1358 and D18S51. The alteration was detected in 47% of cases with larynx carcinoma, 44% of cases with uveal melanoma, 60% of cases with cervical cancers, one case of liposarcoma G3 and one case od neurofibrosarcoma. No LOH was found in liposarcoma G1, dermatofibrosarcoma and cystosarcoma protuberans in either primary or recurrent tumours. In benign tumours (lipoma and fibroma) LOH was also absent. During genotyping of DNA extracted from histopathological tissue sections caution should be taken when non-match or exclusion based on few discrepancies is concluded.

Utility of Circulating Cell-Free DNA in Assessing Microsatellite Instability and Loss of Heterozygosity in Breast Cancer Using Human Identification Approach

“…MSI is characterized by nucleotide gain or loss from short tandem repeat (STR) tracts [7], and manifests as novel alleles of varying length [8] due to a lack of DNA mismatch repair [9,10]. On the other hand, LOH involves one allele mutation, followed by the deletion of the remaining alleles [11], partly due to chromosomal deletion, mitotic recombination (MR), gene conversion, point mutations, or intragenic allelic inactivation [12]. The demonstration of MSI events in primary BC samples, and LOH events in stage II and III cancers, indicates that MSI occurs at early stages of carcinogenesis, in contrast to LOH, which occurs at later stages [13,14].…”

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

“…Zhu et al used LOH analysis to determine that two closely neighbouring HCCs appeared to be intrahepatic metastases of double primary tumours [11] . LOH also has numerous implications for human genetic identification [12] . Frequent allelic loss at chromosomal locations 2q, 3p, 4q, 6p, 6q, 8p, 8q, 9p, 11q, 13q, 14q and 17q is observed in head and neck cancer patients [13] – [16] .…”

Pitfalls in interpreting autosomal InDel markers profiling: A study on mutations in tumoural specimens

“…In special cases, the biological samples that are used for identification purposes can come from tumour biopsies stored in biobanks when they turn out to be the last source of biological material available [6]. Nevertheless, it is known that carcinogenesis is a multistep process in which cells accumulate genetic alterations as they progress to a more malignant phenotype [7,8]. Genomic instability within the tumour tissue can be expressed with different modalities: chromosomal instability (CIN), microsatellite instability (MSI) and instability associated with Nucleotide-Excision Repair (NIN) [9,10].…”