TP53 gene mutation [Neurosurgery Wiki]

This page is read only. You can view the source, but not change it. Ask your administrator if you think this is wrong.
====== TP53 gene mutation ======

[[TP53 gene]] [[mutation]]s are important [[molecular marker]]s in [[diffuse astrocytic tumor]]s and [[medulloblastoma]]s.

TP53 [[gene mutation]]s are very common in human cancers and are the underlying cause of [[Li-Fraumeni syndrome]].
Testing for these is performed by [[polymerase chain reaction]] (PCR).

Whenever possible, appropriate [[molecular genetics]] should also be evaluated. Testing for [[IDH1]] and/or [[IDH2]] mutations should be done in all [[diffuse glioma]]s if possible. Other tests (e.g. 1p/19q co-deletion or TP53 gene mutations) are done as appropriate. 

The combination of [[P53]] and [[IDH1]] as an immunohistochemical panel showed a specificity of 96% and [[sensitivity]] of 91% for [[differential diagnosis]] of [[reactive gliosis]] and [[low-grade astrocytoma]]. These 2 markers can be extremely helpful for this differential diagnosis
((Geramizadeh B, Kohandel-Shirazi M, Soltani A. A Simple Panel of IDH1 and P53 in Differential Diagnosis Between Low-Grade Astrocytoma and Reactive Gliosis. Clin Pathol. 2021 Feb 11;14:2632010X20986168. doi: 10.1177/2632010X20986168. PMID: 33634261; PMCID: PMC7887675.)).
----
see [[Medulloblastoma, SHH-activated, and TP53-mutant]].

see [[Medulloblastoma, SHH-activated, and TP53-wildtype]]
----
[[Li-Fraumeni syndrome]] is usually caused by a [[germline]] [[mutation]] in the [[TP53]] [[tumor suppressor gene]] on [[chromosome 17]]p13.
----


These [[mutation]]s result in a [[p53]] protein that is less able to control [[cell proliferation]]. Specifically, it is unable to trigger [[apoptosis]] in cells with mutated or damaged [[DNA]].
----


[[TP53]] mutations: 27% [[primary glioblastoma]] and in 81 % of [[secondary glioblastoma]]s.
----
The [[TP53 gene]] encodes [[TP53]] ([[tumor protein 53]]), which is a [[tumor suppressor]] that prevents cells from dividing and signals them to undergo [[apoptosis]] if they sustain irreparable [[DNA damage]]. [[TP53 gene mutation]]s are very common in human cancers and are the underlying cause of [[Li-Fraumeni syndrome]].

Testing for these is performed by [[polymerase chain reaction]] ([[PCR]]).

In general, ATRX & TP53 mutations are mutually exclusive of [[1p/19q co-deletion]], and as such may be used as confirmatory markers to distinguish astrocytomas from oligodendrogliomas.

Indications: [[ATRX]] is a confirmatory test along with IDH1 mutation. [[ATRX]] & [[TP53]] can be detected by immunohistochemical (IHC) stains or by [[Fluorescence in situ hybridization]] ([[FISH]]) and may be done in some hospitals or may be sent out to specialty labs; results typically take ≈ 2–3 days. The cost of IHC is on the order of $100–150 U.S., FISH is about $200–250 U.S.

Complete deletion of both the short arm of [[chromosome 1]] (1p) and the long arm of [[chromosome 19]] (19q) is pathognomonic for [[oligodendroglioma]]. It is strongly associated with IDH mutation and is mutually exclusive of [[ATRX]] & [[TP53]] mutations.

[[TP53]] point mutations are found in 50% of all [[cancer]]s and seem to play an important role in [[cancer pathogenesis]]. Thus, [[Human-induced pluripotent stem cell]]s (hiPSCs) overexpressing mutant TP53 are a valuable tool for the generation of [[in vitro]] [[model]]s of [[cancer stem cell]]s or for [[in vivo]] [[xenograft]] models. 
----
[[TP53 mutation]]s appear to be highly represented (> 80%) in all [[gemistocytic astrocytoma]]s, and this is likely to be higher among [[gemistocytic astrocytoma IDH-mutant]].
----
Uhlmann et al. from the [[University Hospital of Düsseldorf]], described a [[protocol]] for the alteration of [[gene expression]] in hiPSCs via overexpression of a mutant form of the TP53 ([[R249S]]) gene using lentiviral transduction. A high amount of TP53 protein is detected 1 week after transduction and antibiotic selection. Differentiation of transduced hiPSCs gives insight into a better understanding of cancer formation in different tissues and may be a useful tool for genetic or pharmacologic screening assays. 

Basic Protocol 1: Production and concentration of third-generation lentivirus Support Protocol 1: Cloning of gene of interest into modulation vector Support Protocol 2: Preparation of DMEM GlutaMAX™ with 10% fetal bovine serum and 1% penicillin-streptomycin Basic Protocol 2: Transduction of human-induced pluripotent stem cells and selection of positively transfected cells Support Protocol 3: Preparation of Matrigel® -coated plates Support Protocol 4: Preparation of mTeSR™1 medium
((Uhlmann C, Kuhn LM, Tigges J, Fritsche E, Kahlert UD. Efficient Modulation of 
TP53 Expression in Human-induced pluripotent stem cells. Curr Protoc Stem Cell
Biol. 2020 Mar;52(1):e102. doi: 10.1002/cpsc.102. PubMed PMID: 31883435.
)).
----
Complete [[deletion]] of both the short arm of [[chromosome 1]] (1p) and the long arm of [[chromosome 19]] ([[19q]]) is pathognomonic for [[oligodendroglioma]]
((Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a sum- mary. Acta Neuropathol. 2016; 131:803–820))
((Stupp R, Brada M, van den Bent MJ, et al. High- grade glioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014; 25 Suppl 3:iii93–ii101))
It is strongly associated with [[IDH mutation]] and is mutually exclusive of [[ATRX]] & [[TP53]] [[mutation]]s.

===== References =====