Subject(s)
Brain Neoplasms , Colorectal Neoplasms , DNA Mismatch Repair/genetics , Neoplastic Syndromes, Hereditary , Adolescent , Brain Neoplasms/diagnosis , Brain Neoplasms/genetics , Brain Neoplasms/therapy , Child , Colonoscopy , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/genetics , Colorectal Neoplasms/therapy , DNA Polymerase II/genetics , DNA Polymerase III/genetics , Diagnosis, Differential , Genetic Counseling , Germ-Line Mutation , Guidelines as Topic , Humans , Immune Checkpoint Inhibitors/therapeutic use , Li-Fraumeni Syndrome/psychology , Lupus Erythematosus, Systemic/genetics , Neoplastic Syndromes, Hereditary/diagnosis , Neoplastic Syndromes, Hereditary/genetics , Neoplastic Syndromes, Hereditary/therapy , Netherlands , Poly-ADP-Ribose Binding Proteins/genetics , Vaccination , Young AdultABSTRACT
Tackling the topic of genetic predisposition to childhood cancer requires close co-operation between pathologists, pediatric oncologists, and human geneticists. It is not just about the precise diagnosis and the most effective treatment of the cancer, but also to prevent further cancerous diseases for those affected and also their family members. On the basis of examples such as Li-Fraumeni syndrome, constitutional mismatch repair deficiency (CMMRD), medullo- and neuroblastoma, as well as hematological neoplasias, we will discuss the criteria for tumor predisposition genetic syndromes, the relationship between somatic and germline variants, and the immediate clinical consequences. In some cases, the diagnosis of a genetic tumor predisposition syndrome has immediate consequences for the treatment, e.â¯g. to avoid radiotherapy for Li-Fraumeni syndrome, which would otherwise significantly increase the probability of secondary, independent tumors. Predictive diagnostics can be offered to identify the family members who carry the pathogenic variant. Because of their increased tumor risk, they should be integrated into cancer surveillance programs. Evidence-based data show that this significantly improves overall survival.
Subject(s)
Brain Neoplasms , Colorectal Neoplasms , Genetic Predisposition to Disease , Hematologic Neoplasms , Neoplastic Syndromes, Hereditary , Child , Germ-Line Mutation , HumansABSTRACT
Combining fluorescence R-banding, fluorescence in situ hybridization and spectral karyotyping allowed us to precisely define chromosomal breakpoints, gains, losses and a newly detected amplification in the human mantle cell lymphoma (MCL) cell line GRANTA-519. GRANTA-519 is characterized by the t(11;14)(q13;q32) resulting in overexpression of cyclin D1, a key player in cell cycle control. Hitherto unresolved complex rearrangements involve 1p, 1q, 3cen, 9p, 11q, 12p, 12q, 16p, 17p, and 18cen. Moreover, a 4- to 6-fold gain of sequences on 18q leads to a low-level amplification of the BCL2 gene and to an overexpression of the BCL2 protein. These results provide the basis for the identification of not only candidate oncogenes responsible for MCL in gained regions, but also for the identification of putative tumor suppressor genes in commonly deleted regions like 1p22, which would eventually enable functional studies of these genes.
