Changes

Translocation/Fusion

Translocation/Fusion

In some cases (eg, like TP53) this may not help the user much, as TP53 mutations encompasses all types.

In an example for TP53, there are two short paragraphs followed by a table.  This is appropriate, becasue TP53 is found in a vast number of different cancers.

 

The ''TP53'' gene contains homozygous mutations in about 50-60% of human cancers. About 90% of the mutations in ''TP53'' encode missense mutant proteins that span about 190 codons in the DNA-binding domain; none of the 50 most common pathogenic missense mutations occur outside of the DNA-binding region. These mutations produce a protein with a reduced capacity to bind to a specific DNA sequence that regulates p53 transcriptional pathway [15]. The eight most common mutations across all cancer types (R175H, R248Q, R273H, R248W, R273C, R282W, G245S, R249S) are found in codons that account for about 28% of the total p53 mutations (See Table 1 in [15]); these alleles appear to be selected for preferentially in human cancers of many tissue types. Seven of the eight mutations occur at methylated CpG sites in ''TP53'', which encode arginine residues that contact the DNA and are conserved over evolutionary time scales [15].

 

 

Inactivating mutations resulting in loss of p53 function, including deletions, LOH, and loss of function (LOF) alterations often confer a poor prognosis and chemoresistance.  Alternatively, gain-of-function mutations promoting the expression and stability of the p53 protein in the nucleus can also lead to oncogenic effects, including genomic instability and excessive cell proliferation [12].

{| class="wikitable sortable"

{| class="wikitable sortable"

! Copy Number Loss  !! Copy Number Gain  !!  LOH  !!  Loss-of-Function Mutation  !!  Gain-of-Function Mutation  !!  Translocation/Fusion  

! Copy Number Loss  !! Copy Number Gain  !!  LOH  !!  Loss-of-Function Mutation  !!  Gain-of-Function Mutation  !!  Translocation/Fusion  

|-

|-

| EXAMPLE: X ||EXAMPLE: X || EXAMPLE: X || EXAMPLE: X || EXAMPLE: X || EXAMPLE: X

| X ||  || X || X || X ||

|}

|}

However, in many cases, these types of tables are useful to a user. In the example of RUNX1, by far the most frequent mutations are fusion genes which are loss of function mutations. See the example below.

In the example of RUNX1, the two most common cancers associated to RUNX1 mutations are listed, along with the most common fusion genes assocaited, followed by a table.

 

 

'''Acute Myeloid Leukemia (AML);'''    t(8;21)(q22;q22) resulting in RUNX1-RUNX1T1 fusion

'''Acute Myeloid Leukemia (AML);'''    t(8;21)(q22;q22) resulting in RUNX1-RUNX1T1 fusion