Association of <i>TP53</i> Alteration with Tissue Specificity and Patient Outcome of <i>IDH1</i>-Mutant Glioma
Since the initial discovery of recurrent isocitrate dehydrogenase 1 (<i>IDH1)</i> mutations at Arg132 in glioma, <i>IDH1</i> hotspot mutations have been identified in cholangiocarcinoma, chondrosarcoma, leukemia, and various other types of cancer of sporadic incidence. Studie...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-08-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/10/8/2116 |
| _version_ | 1797524316125921280 |
|---|---|
| author | Balazs Murnyak L. Eric Huang |
| author_facet | Balazs Murnyak L. Eric Huang |
| author_sort | Balazs Murnyak |
| collection | DOAJ |
| description | Since the initial discovery of recurrent isocitrate dehydrogenase 1 (<i>IDH1)</i> mutations at Arg132 in glioma, <i>IDH1</i> hotspot mutations have been identified in cholangiocarcinoma, chondrosarcoma, leukemia, and various other types of cancer of sporadic incidence. Studies in glioma and leukemia have helped promote the theory that <i>IDH1</i> mutations are an oncogenic event that drives tumorigenesis in general. Through bioinformatic analysis of more than 45,000 human pan-cancer samples from three independent datasets, we show here that <i>IDH1</i> mutations are rare events in human cancer but are exclusively prevalent in WHO grade II and grade III (lower-grade) glioma. Interestingly, alterations in the tumor-suppressor gene <i>TP53</i> (tumor protein p53) co-occur significantly with <i>IDH1</i> mutations and show a tendency of exclusivity to <i>IDH2</i> mutations. The co-occurrence of <i>IDH1</i> mutation and <i>TP53</i> alteration is widespread in glioma, particularly in those harboring <i>IDH1<sup>R132H</sup></i>, <i>IDH1<sup>R132G</sup></i>, and <i>IDH1<sup>R132S</sup></i>, whereas co-occurrence of <i>IDH1<sup>R132C</sup></i> and <i>TP53</i> alteration can be found sporadically in other cancer types. In keeping with the importance of p53 in tumor suppression, <i>TP53</i> status is an independent predictor of overall survival irrespective of histological and molecular subgroups in lower-grade glioma. Together, these results indicate tissue specificity of <i>IDH1</i> hotspot mutation and <i>TP53</i> alteration and the importance of <i>TP53</i> status as a predictor of patient outcome in lower-grade glioma. |
| first_indexed | 2024-03-10T08:55:37Z |
| format | Article |
| id | doaj.art-86946ef108004f569182b68c5e1aa145 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T08:55:37Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-86946ef108004f569182b68c5e1aa1452023-11-22T07:11:58ZengMDPI AGCells2073-44092021-08-01108211610.3390/cells10082116Association of <i>TP53</i> Alteration with Tissue Specificity and Patient Outcome of <i>IDH1</i>-Mutant GliomaBalazs Murnyak0L. Eric Huang1Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake City, UT 84132, USADepartment of Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake City, UT 84132, USASince the initial discovery of recurrent isocitrate dehydrogenase 1 (<i>IDH1)</i> mutations at Arg132 in glioma, <i>IDH1</i> hotspot mutations have been identified in cholangiocarcinoma, chondrosarcoma, leukemia, and various other types of cancer of sporadic incidence. Studies in glioma and leukemia have helped promote the theory that <i>IDH1</i> mutations are an oncogenic event that drives tumorigenesis in general. Through bioinformatic analysis of more than 45,000 human pan-cancer samples from three independent datasets, we show here that <i>IDH1</i> mutations are rare events in human cancer but are exclusively prevalent in WHO grade II and grade III (lower-grade) glioma. Interestingly, alterations in the tumor-suppressor gene <i>TP53</i> (tumor protein p53) co-occur significantly with <i>IDH1</i> mutations and show a tendency of exclusivity to <i>IDH2</i> mutations. The co-occurrence of <i>IDH1</i> mutation and <i>TP53</i> alteration is widespread in glioma, particularly in those harboring <i>IDH1<sup>R132H</sup></i>, <i>IDH1<sup>R132G</sup></i>, and <i>IDH1<sup>R132S</sup></i>, whereas co-occurrence of <i>IDH1<sup>R132C</sup></i> and <i>TP53</i> alteration can be found sporadically in other cancer types. In keeping with the importance of p53 in tumor suppression, <i>TP53</i> status is an independent predictor of overall survival irrespective of histological and molecular subgroups in lower-grade glioma. Together, these results indicate tissue specificity of <i>IDH1</i> hotspot mutation and <i>TP53</i> alteration and the importance of <i>TP53</i> status as a predictor of patient outcome in lower-grade glioma.https://www.mdpi.com/2073-4409/10/8/2116gliomaIDHisocitrate dehydrogenasepan-cancerpatient outcomesurvival |
| spellingShingle | Balazs Murnyak L. Eric Huang Association of <i>TP53</i> Alteration with Tissue Specificity and Patient Outcome of <i>IDH1</i>-Mutant Glioma Cells glioma IDH isocitrate dehydrogenase pan-cancer patient outcome survival |
| title | Association of <i>TP53</i> Alteration with Tissue Specificity and Patient Outcome of <i>IDH1</i>-Mutant Glioma |
| title_full | Association of <i>TP53</i> Alteration with Tissue Specificity and Patient Outcome of <i>IDH1</i>-Mutant Glioma |
| title_fullStr | Association of <i>TP53</i> Alteration with Tissue Specificity and Patient Outcome of <i>IDH1</i>-Mutant Glioma |
| title_full_unstemmed | Association of <i>TP53</i> Alteration with Tissue Specificity and Patient Outcome of <i>IDH1</i>-Mutant Glioma |
| title_short | Association of <i>TP53</i> Alteration with Tissue Specificity and Patient Outcome of <i>IDH1</i>-Mutant Glioma |
| title_sort | association of i tp53 i alteration with tissue specificity and patient outcome of i idh1 i mutant glioma |
| topic | glioma IDH isocitrate dehydrogenase pan-cancer patient outcome survival |
| url | https://www.mdpi.com/2073-4409/10/8/2116 |
| work_keys_str_mv | AT balazsmurnyak associationofitp53ialterationwithtissuespecificityandpatientoutcomeofiidh1imutantglioma AT lerichuang associationofitp53ialterationwithtissuespecificityandpatientoutcomeofiidh1imutantglioma |