Epigenetic profiling to classify cancer of unknown primary: a multicentre, retrospective analysis

Details matter: the role of genomic location and assay standardization in DNA methylation analyses

“…This hypomethylation, frequently seen early in cancer development, is commonly followed by locus-specific hypermethylation. Large-scale analyses have shown that DNA methylation aberrations are frequently present in cancers [9] and that DNA methylation profiling enables distinguishing cancer subtypes [10] and classifying cancers of unknown primary origin [11].A variety of DNA methylation aberrations have been suggested as biomarkers for early detection, prognostication and monitoring of cancer, including in noninvasive clinical material such as blood, stool, urine and bile. Great hopes are also tied to DNA methylation as a direct target for epigenetic therapy.…”

“…This hypomethylation, frequently seen early in cancer development, is commonly followed by locus-specific hypermethylation. Large-scale analyses have shown that DNA methylation aberrations are frequently present in cancers [9] and that DNA methylation profiling enables distinguishing cancer subtypes [10] and classifying cancers of unknown primary origin [11].…”

CUP Syndrome

“…Molecular tumor profiling (MTP) kits for this are commercially available that use RNA or DNA similarity analyses to identify the primary tumor (15). Additionally, analyses using multiple epigenetic alterations (e.g., the methylation profile of metastases) to identify the primary tumor have recently been published (16,17).…”

“…This can be followed by a tumor-specific therapy to improve prognosis of patients with clinically-defined CUP syndrome (16,27). Also, the demonstration of potentially targeted, oncogenic driver mutations offers a possible treatment approach that is independent of the primary tumor (28,29).…”

Cancer detection and tissue of origin determination with novel annotation and scoring of cell-free methylated DNA

“…Specific patterns of DNA methylation are frequently characteristic of a given tissue. Consequently, analysing the DNA methylation pattern of a length of DNA can be used to predict from which tissue it originated (6). In addition to the mutational changes affecting the cancer genome, the DNA methylation patterns of cancer cells are highly disrupted, undergoing a global loss of DNA methylation as well as hypermethylation in specific regions including some tumour suppressor genes (7).…”