Epigenetic signatures in gastric cancer: current knowledge and future perspectives.

INTRODUCTION: Gastric cancer (GC) is the fifth most common malignancy in the world and accounts for 7.7% of all cancer-related deaths. Early diagnosis of GC is critical in terms of prognosis, and aberrations at the molecular level, especially epigenetic alterations, manifest much earlier than histological findings. In recent years, there has been a great deal of research on the epigenomic profile of GC, and epigenetic alterations seem to play a more important role than genetic factors. With the introduction of epigenetic drugs into clinical use in the last decade, the importance of the epigenetic background of GC has increased considerably. AREAS COVERED: In this review, we summarize the role of methylation changes, histone modifications, and non-coding RNAs in the pathogenesis of GC and how these signatures can be used as diagnostic and therapeutic targets in clinical management. EXPERT OPINION: Epigenetic alterations take place before most genetic aberrations observed in GC and may have an initiating role in the pathogenesis of GC. They can be used as biomarkers in risk calculation, early diagnosis, and evaluation of prognosis of GC, as well as treatment targets.

Complex karyotype with double Philadelphia chromosome and T315I mutation results in blastic phase and extensive extramedullary infiltration in a chronic myeloid leukemia patient.

Chronic myeloid leukemia (CML) is a common hematological malignancy originating from bone marrow stem cells. Chromosomal abnormalities can be seen in almost all cases, the most known anomaly being Philadelphia (Ph) chromosome, a derivative chromosome resulting from a translocation between 9. and 22. chromosome. Other chromosomal abnormalities may be present in 10% of patients at diagnosis, although they emerge frequently during the acute transformation and can be associated with unfavorable significance. Also, point mutations like T315I in BCR-ABL fusion gene may arise during the course of the disease and thereby cause tyrosine kinase inhibitors (TKI) resistance. Here, we report a BCR-ABL positive CML patient who was followed for 6 years in major molecular response (MMR), complete cytogenetic response (CCR), and complete hematological response (CHR). He had a sudden loss of hematological, cytogenetic, and molecular response with a very aggressive blastic course and extensive extramedullary infiltration, with T315I mutation, complex translocations, an extra Ph chromosome, and additional chromosomes. The patient who received intensive cytotoxic chemotherapy together with ponatinib treatment, which is effective for the T315I mutation, never went into remission, and there was no chance of transplantation because a suitable donor for HLA could not be found. Although these findings are not very rare individually, coexistence of complex karyotype and T315I mutation is not frequent and complicates clinical management. Our patient is the first case in literature with all disclosed findings together and indicates the importance of early detection of these chromosomal and molecular abnormalities.