Changes

''TP53'' mutations have been associated with ''IDH1''-mutated astrocytoma and glioblastoma more than with other glioma subtypes [20,59], and astrocytomas are thought to develop via ''TP53'' and ''ATRX'' mutations subsequent to ''IDH1'' mutations. Astrocytomas associated with germline ''TP53'' mutations were found to have somatic ''IDH1'' Arg123Cys (NM_005896.2/NP_005887.2) mutations which are otherwise rare in this malignancy, suggesting the preferential occurrence of this specific mutation in cells that already contain a ''TP53'' mutation [60].

''TP53'' mutations have been associated with ''IDH1''-mutated astrocytoma and glioblastoma more than with other glioma subtypes [20,59], and astrocytomas are thought to develop via ''TP53'' and ''ATRX'' mutations subsequent to ''IDH1'' mutations. Astrocytomas associated with germline ''TP53'' mutations were found to have somatic ''IDH1'' Arg123Cys (NM_005896.2/NP_005887.2) mutations which are otherwise rare in this malignancy, suggesting the preferential occurrence of this specific mutation in cells that already contain a ''TP53'' mutation [60].

Loss of chromosome arms 1p and 19q is observed more frequently in oligodendroglial tumours with ''IDH1'' mutations compared to other ''IDH1''-mutated or ''IDH1'' wild-type gliomas [20]. Oligodendrogliomas often develop mutations in the ''TERT'' promoter in addition to 1p/19q deletions after ''IDH1'' mutation[61], and these are thought to be important events in their developmental pathway.  

Loss of chromosome arms 1p and 19q is observed more frequently in oligodendroglial tumours with ''IDH1'' mutations compared to other ''IDH1''-mutated or ''IDH1'' wild-type gliomas [20]. Oligodendrogliomas often develop mutations in the ''TERT'' promoter in addition to 1p/19q deletions after ''IDH1'' mutation [61], and these are thought to be important events in their developmental pathway.  

Other genetic changes common to glioma such as epidermal growth factor receptor (''EGFR'') amplification, cyclin-dependent kinase inhibitor 2A or 2B (''CDKN2A/2B'') deletion, and phosphatase or tensin homolog (''PTEN'') mutations occur less frequently in IDH1-mutated malignancies compared to those with wild-type IDH1 [20].

Other genetic changes common to glioma such as epidermal growth factor receptor (''EGFR'') amplification, cyclin-dependent kinase inhibitor 2A or 2B (''CDKN2A/2B'') deletion, and phosphatase or tensin homolog (''PTEN'') mutations occur less frequently in ''IDH1''-mutated malignancies compared to those with wild-type ''IDH1'' [20].

In AML, ''IDH1'' mutations are associated with ''NPM1'' mutations but show negative association with ''CEBPA'' and ''WT1'' mutations[62]. Patients with ''IDH1'' mutations also have a lower frequency of FLT3-ITD mutations and are generally associated with a molecular low-risk group (''NPM1''-mutated and FLT3-ITD-negative)63 and normal cytogenetics [64].

In AML, ''IDH1'' mutations are associated with ''NPM1'' mutations but show negative association with ''CEBPA'' and ''WT1'' mutations [62]. Patients with ''IDH1'' mutations also have a lower frequency of ''FLT3''-ITD mutations and are generally associated with a molecular low-risk group (''NPM1''-mutated and ''FLT3''-ITD-negative) [63] and normal cytogenetics [64].

===Therapeutic Implications===

===Therapeutic Implications===