Hereditary cancer syndromes(HCSs)are arguably the most frequent category of Mendelian genetic diseases,as at least 2%of presumably healthy subjects carry highly-penetrant tumor-predisposing pathogenic variants(PVs).He...Hereditary cancer syndromes(HCSs)are arguably the most frequent category of Mendelian genetic diseases,as at least 2%of presumably healthy subjects carry highly-penetrant tumor-predisposing pathogenic variants(PVs).Hereditary breast-ovarian cancer and Lynch syndrome make the highest contribution to cancer morbidity;in addition,there are several dozen less frequent types of familial tumors.The development of the majority albeit not all hereditary malignancies involves two-hit mechanism,i.e.the somatic inactivation of the remaining copy of the affected gene.Earlier studies on cancer families suggested nearly fatal penetrance for the majority of HCS genes;however,population-based investigations and especially large-scale next-generation sequencing data sets demonstrate that the presence of some highly-penetrant PVs is often compatible with healthy status.Hereditary cancer research initially focused mainly on cancer detection and prevention.Recent studies identified multiple HCS-specific drug vulnerabilities,which translated into the development of highly efficient therapeutic options.展开更多
基金Supported by The Russian Science Foundation,No.17-75-30027。
文摘Hereditary cancer syndromes(HCSs)are arguably the most frequent category of Mendelian genetic diseases,as at least 2%of presumably healthy subjects carry highly-penetrant tumor-predisposing pathogenic variants(PVs).Hereditary breast-ovarian cancer and Lynch syndrome make the highest contribution to cancer morbidity;in addition,there are several dozen less frequent types of familial tumors.The development of the majority albeit not all hereditary malignancies involves two-hit mechanism,i.e.the somatic inactivation of the remaining copy of the affected gene.Earlier studies on cancer families suggested nearly fatal penetrance for the majority of HCS genes;however,population-based investigations and especially large-scale next-generation sequencing data sets demonstrate that the presence of some highly-penetrant PVs is often compatible with healthy status.Hereditary cancer research initially focused mainly on cancer detection and prevention.Recent studies identified multiple HCS-specific drug vulnerabilities,which translated into the development of highly efficient therapeutic options.
