V. Koneti Rao, United States of America
National Institutes of Health LCIM/NIAIDPresenter of 1 Presentation
RISK OF LYMPHOMA AND OTHER CANCERS ASSOCIATED WITH IMMUNE-DYSREGULATION AND LYMPHOPROLIFERATION AND ITS GENETIC UNDERPINNINGS: SCALING BEYOND ALPS
Abstract
Background and Aims
The term Hodgkin’s disease like Virchow’s subsequent term lymphoma was named after Thomas Hodgkin in 1832 to designate swollen lymph nodes of unknown cause("neoplasm"). Lymphoma is a malignant neoplasm of the immune system. Innate and adaptive immune responses are dependent on lymphocyte ontogeny and location based proteins triggered by many genes including receptors and regulators. Epidemiology of lymphoid neoplasia includes auto-inflammation, chronic infections, antigen stimulation, oncogenic viruses, proliferation/apoptosis, immune check point imbalance, chemical and environmental exposure as well as genetic background. Recent advances in the diagnostic genomics have led to identification of many new germline and somatic genetic syndromes of immune dysregulation orchestrating the interplay between nonmalignant lymphoproliferation and lymphoma.
Methods
The cancer and lymphoma susceptibility lessons learnt from ALPS-FAS (Autoimmune Lymphoproliferative Syndrome) and RALD (RAS Associated Leukoproliferative Disorder) over many years can be used as a paradigm for lymphoma risk assessment in many recently described genetic disorders of immune system including CTLA4 haploinsufficiency, PIK3CD, and MagT1defects (XMEN).
Results
Diligent long term follow up at NIHCC with subspecialist collaboration fostered critical thinking needed for diagnosis and management of these immune-mediated lymphoma predisposition syndromes. Rare genetic disorders elucidate the critical immune surveillance pathways to malignant neoplasia and help us to treat them better with targeted therapeutics.
Conclusions
Studying patients with germline and somatic genetic variants leading to immunedysregulation and cancer susceptibility, profiling both germline and tumor DNA in all cancer patients at diagnosis should provide tools towards better patient care through early anticipation, diagnosis, management and prevention of malignancies within the affected families and general population.