A critical evaluation of loss of heterozygosity detected in tumor tissues, blood serum and bone marrow plasma from patients with breast cancer

Abstract

Introduction The aim of the study was to perform a comparative analysis of LOH (loss of heterozygosity) in primary tumors as well as peripheral blood and bone marrow (BM) of patients with breast cancer (BCa).

Loss of Heterozygosity at Tumor Suppressor Genes Detectable on Fractionated Circulating Cell-Free Tumor DNA as Indicator of Breast Cancer Progression

“…The gene product of this tumor suppressor gene has been involved in a number of cellular processes including DNA repair and recombination, cell-cycle checkpoint control, chromatin remodeling, ubiquitination, and apoptosis (26). Deletions of BRCA1 have recently been implicated in local recurrence and bad prognosis (10,(27)(28)(29). Because repression of BRCA1 may cause increased genomic instability, its loss may contribute to the aggressive features of HER2-positive breast tumors.…”

“…It has been reported that RB1 gene is inactivated in about 20% of breast carcinomas (39). Genetic aberrations of this region have been described to frequently occur in breast cancer and to associate with tumor progression, poor prognosis (10,40), and especially with the inability of cells to differentiate (39). RB1 acts as a master regulator by interacting and controlling numerous proteins.…”

“…Generally, the number of LOH detected in plasma or serum was lower than in the paired tumor tissues (10). The contradictory microsatellite data derived from blood and tumor tissue might be caused by the low prevalence of tumor-derived DNA in blood of patients with cancer (4,10,11). Apart from killing of neoplastic cells, necrosis may also cause death of stromal cells surrounding the primary tumor.…”

“…Besides the described concordances between LOH on plasma/serum DNA and LOH in the matched primary tumors, also discrepancies were discovered (4). Generally, the number of LOH detected in plasma or serum was lower than in the paired tumor tissues (10). The contradictory microsatellite data derived from blood and tumor tissue might be caused by the low prevalence of tumor-derived DNA in blood of patients with cancer (4,10,11).…”

Review: Biological relevance of disseminated tumor cells in cancer patients

“…1,10,11 Another possible confounder is the fact that DNA molecules are relatively stable, and therefore the detection of tumor specific genomic aberrations may not necessarily indicate the presence of intact DTC but also DNA fragments derived from necrotic or apoptotic tumor cells. [40][41][42] Therefore, measurements of epithelium-specific or more organspecific mRNA species such as CK19 and 20 or mammaglobin or PSA mRNA by RT (reverse transcriptase)-PCR have been proven as more promising to detect DTC in BM samples. [43][44][45][46][47][48][49][50] The main advantage of very sensitive RT-based techniques for the detection of DTC at the single-cell level is the nearly ''unlimited'' availability of primers for almost every gene of interest.…”