# Ras Isoforms from Lab Benches to Lives--What Are We Missing and How Far Are We?
## 2 Ras in Cancers  
Ras is mutated in \(\sim\)30% of cancers. Against the previous belief of p21 Ras as a single oncogenic entity, newer studies associated Ras isoforms with specific types of cancers. K-Ras mutations are the major contributors to most cancers. H-Ras mutation leads to cancers of the skin, head, and neck involving cutaneous squamous cells, whereas K-Ras is highly mutated in pancreatic, colorectal cancers, and adenocarcinoma of the lungs. N-Ras is frequently mutated in leukemias of myeloblastic cell type [25] and is implicated in myelodysplastic syndromes [26]. Oncogenic mutations frequently occur at residues 12, 13, 59, 61, and 63 impairing the GAPs mediated GTP hydrolysis to result in constitutively active Ras. As per the Cancer Genome Atlas (TCGA) project in 46% of cancers, the receptor tyrosine kinase-Ras pathway is altered [27]. Table 1 shows the percentage of point mutations in Ras isoforms in different primary tissues.  
\begin{table}
\begin{tabular}{c c c c c c c c} \hline \hline \multirow{2}{*}{**S. No.**} & \multirow{2}{*}{\begin{tabular}{c} **Primary Tissue** \\ **Type** \\ \end{tabular} } & \multirow{2}{*}{\begin{tabular}{c} **(Mutated)** \\ **Total Samples** \\ **Tested** \\ \end{tabular} } & \multirow{2}{*}{\begin{tabular}{c} **(Mutations)** \\ **\% of Point** \\ **Mutations** \\ \end{tabular} } & \multirow{2}{*}{\begin{tabular}{c} **(Mutated)** \\ **Total Samples** \\ **Tested** \\ \end{tabular} } & \multirow{2}{*}{\begin{tabular}{c} **\% of Point** \\ **Mutations** \\ \end{tabular} } & \multirow{2}{*}{\begin{tabular}{c} **(Mutations)** \\ **Tested** \\ \end{tabular} } & \multirow{2}{*}{\
\begin{tabular}{c} **(Mutated)** \\ **Total Samples** \\ **Tested** \\ \end{tabular} } & \multirow{2}{*}{
\begin{tabular}{c} **\% of Point** \\ **Mutations** \\ \end{tabular} } \\ \hline  & & H-Ras & K-Ras & K-Ras & N-Ras & N-Ras \\ \hline
1 & Adrenal gland & (45)1303 & 3.45 & (1)1331 & 0.88 & (13)1276 & 1.02 \\ \hline
2 & Autonomic ganglia & (6)1597 & 0.38 & (1)1572 & 0.06 & (11)1673 & 0.66 \\ \hline
3 & Biliary tract & (9)1728 & 0.52 & (958)5367 & 19.49 & (58)2133 & 2.72 \\ \hline
4 & Bone & (8)1060 & 0.75 & (14)1184 & 1.27 & (13)1209 & 1.08 \\ \hline
5 & Breast & (54)8192 & 0.66 & (150)11297 & 1.42 & (33)7763 & 0.43 \\ \hline
6 &
\begin{tabular}{c} Central nervous \\ system \\ \end{tabular} & (11)4150 & 0.27 & (47)4881 & 1.21 & (54)4800 & 1.13 \\ \hline
7 & Cervix & (28)1249 & 2.24 & (151)2569 & 6.03 & (10)1191 & 0.84 \\ \hline
8 & Endometrium & (14)2384 & 0.59 & (720)4663 & 15.89 & (53)1637 & 3.24 \\ \hline
9 & Eye & 340 & \(-\) & (7)476 & 1.47 & (40)888 & 4.5 \\ \hline
10 & Fallopian tube & 3 & \(-\) & 9 & \(-\) & 6 & \(-\) \\ \hline
11 &
\begin{tabular}{c} Female genital tract \\ (site indeterminate) \\ \end{tabular} & 20 & \(-\) & (1)24 & 8.33 & 22 & \(-\) \\ \hline
12 &
\begin{tabular}{c} Gastrointestinal tract \\ (site indeterminate) \\ \end{tabular} & 1 & \(-\) & (70)1083 & 6.46 & 477 & \(-\) \\ \hline
13 & Genital tract & (2)285 & 0.7 & (36)576 & 6.42 & (12)565 & 2.12 \\ \hline
14 &
\begin{tabular}{c} Haematopoietic and \\ lymphoid \\ \end{tabular} & (24)12623 & 0.19 & (1124)24788 & 4.91 & (2517)28829 & 8.73 \\ \hline
15 & Kidney & (7)31127 & 0.22 & (41)4277 & 1.01 & (12)3345 & 0.36 \\ \hline
16 & Large intestine & (56)5989 & 0.94 & (25902)80015 & 33.4 & (617)16211 & 3.81 \\ \hline
17 & Liver & (7)2902 & 0.24 & (112)(3604 & 3.3 & (34)3164 & 1.07 \\ \hline
18 & Lung & (45)7450 & 0.6 & (6419)43284 & 16.08 & (145)16486 & 0.88 \\ \hline
19 & Mediastinum & 1 & \(-\) & 1 & \(-\) & 1 & \(-\) \\ \hline \hline \end{tabular}
\end{table}
Table 1: The table has been compiled using data from COSMIC v92 (Catalog Of Somatic Mutations In Cancer by Sangers Institute ([[https://cancer.sanger.ac.uk/cosmic](https://cancer.sanger.ac.uk/cosmic)]([https://cancer.sanger.ac.uk/cosmic](https://cancer.sanger.ac.uk/cosmic)), accessed on 13 June 2021)).