Short communication
JBS. 2016 Dec.; 3(4):35-37
Journal of Biomedical Sciences
Official Publication of NHRWS
Oncogenes – the basics
Arnab Ghosh, Dilasma Ghartimagar, Sushma Thapa
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Ghosh A, Ghartimagar D, Thapa S. Oncogenes - the basics. Journal of Biomedical Sciences.
2016;3(4):35-37.
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SHORT COMMUNICATION
Oncogenes – the basics
Ghosh A1, Ghartimagar D2, Thapa S3
Correspondence to:
docarnab2k@yahoo.com Normal cell cycle and cell proliferation are regulated by
several genes which can be broadly classified into 4 groups
1
Dr. Arnab Ghosh, Professor, Department of Pathology, viz, proto-oncogenes, tumor suppressor genes, genes
Manipal College of Medical Sciences, Pokhara, Nepal. regulating apoptosis and genes involved in DNA repair. These
genes may be defective due to different factors. The defective
2
Dr. Dilasma Ghartimagar, Associate Professor, genes may lead to production of abnormal proteins which
Department of Pathology, Manipal College of Medical may lead to disruption of the normal cell cycle and
Sciences, Pokhara, Nepal. proliferation. A single precursor cell with defective gene
proliferates surpassing the normal physiologic regulatory
3
Dr. Sushma Thapa, Lecturer , Department of Pathology, process and leads to tumor formation, so, traditionally,it is
Manipal College of Medical Sciences, Pokhara, Nepal. said that “tumors are clonal” [1-3].
Proto-oncogene is a normal gene, which turns defective due
to chromosomal rearrangements (e.g., chromosomal
Information about the article inversions, translocations etc), mutations, or gene
amplifications and leads to the formation of “oncogenes”.
Received: Oct. 25, 2017
Revised: Jan. 30, 2018 These oncogenes function autonomously and encode
Accepted: Feb. 21, 2018 defective proteins with erroneous function which affect the
Published online: May. 18, 2018 cell regulation in a detrimental way. Usually the encoded
protein has excessive normal function or acquires a new
function. That is why, these mutations are also called as “gain
of function” mutations. Similarly, mutations in tumor
suppressor genes also alter the normal cell proliferation but
these mutations cause “loss of function” of the encoded
proteins. The third group of genes which regulate apoptosis,
after mutation, causes inhibition of apoptosis leading to
increased survival of the cells. The last group of genes which
repair any accidental defect in the DNA during cell division
may lose their normal function once they are mutated [1].
Mutations can be in the germ line and thus hereditary or they
can be acquired due to known ( e.g., environmental factors ,
viral infections) or unknown causes. In carcinogesis, most of
the mutations are of acquired type [4].
As it was mentioned, oncogenes ( the altered activated proto-
oncogenes ) lead to encoding of defective proteins which are
known as oncoprotiens. These oncoproteins affect the
normal cell cycle and enhance the proliferation of the cells.
Normally cell proliferation includes a multistep sequential
process involving several proteins and interestingly,
oncogenes can affect any or several of these steps. In normal
physiologic cell proliferation, growth factors bind to growth
factor receptors on the cell surface leading to activation of
several intracellular signalling pathways in the cytoplasm,
which in turn induce and activate regulatory proteins in the
nucleus. These activated nuclear factors initiate DNA
transcription [1, 3].
JBS 2016;3(4):35-37
Journal of Biomedical Sciences Oncogenes – the basics
Table - 1 Examples of a few oncoproteins, its types and related malignancies [1, 5]
Type Oncogene Related Malignancies
Growth factor PDGF – β PDGFB Astrocytoma
Fibroblast growth factor FGF3 Stomach, Urinary bladder, Breast carcinomas, Melanoma
Growth factor EGF receptor ERBB1 (EGFR) Adenocarcinoma of Lung
receptor EGF receptor ERBB2 (HER) Breast carcinoma
Receptor for neurotrophic factor RET Familial medullary thyroid carcinoma
PDGF receptor PDGFRB Glioma, Leukemia
Receptor for KIT ligand KIT Gastrointestinal stromal tumor(GIST)
ALK receptor ALK Adenocarcinoma lung, certain Lymphoma, Neuroblastoma
Signal transduction GTP binding protein KRAS Colon, Lung, Pancreas carcinoma
pathway Tyrosine kinase ABL Chronic myelogenousleukemia(CML), Acute lymphoblastic
leukemia ( ALL)
RAS signal transduction BRAF Melanoma, Leukemias
JAK/STAT signal transduction JAK2 ALL, Myeloproliferative disorder
Nuclear regulatory Transcriptional activator MYC Burkitt lymphoma
protein NMYC Neuroblastoma
Cell cycle regulator Cyclin Cyclin D1 Mantle cell lymphoma, Multiple myeloma
Cyclin dependent kinase CDK4 Gliobllastoma, Melanoma
There are several subtypes of growth factors, surface Table - 2 A few examples of therapeutic drugs and
receptors, proteins involved in intra-cytoplasmic pathways related oncogenes [4].
and intra-nuclear proteins. These processes ultimately lead to Drugs Oncoprotein Related malignancies
progression of a cell in the cell cycle and further cell division. Trastuzumab ERBB2 (HER) Breast
Cell cycles are regulated by cyclins, cyclin dependent kinases (Herceptin)
Cetuximab EGFR Colorectal
and inhibitors. As the above multistep processes involve
Imatinib ABL, KIT, PDGFR CML, GIST
several subtypes of proteins or factors, mutated protein (Gleevec)
counterparts or oncoproteins too can be of several subtypes Gefitinib EGFR Lung ( non small cell
and lead to increased number of mutated cells [1-3]. carcinoma)
Oncoproteins can also affect other processes besides cell Erlotinib EGFR Lung ( non small cell
carcinoma)
cycle, e.g., angiogenesis in tumor, metastasis etc. [1]. Some of
Sorafenib VEGFR, PDGFR, Renal cell carcinoma(RCC)
the oncogenes, its type and the related cancer have been FLT3
depicted in Table 1 [1, 5]. Sumatinib VEGFR, PDGFR, RCC, GIST
The initial genetic alteration “initiates” the process of tumor FLT3
formation or carcinogenesis. It was seen in experimental
models as well as in some malignancies that tumors may Carcinogenesis is an evolving subject with many ongoing
behave differently with time, for example, it may become researches across the globe, ever changing concepts and
suddenly aggressive or the response to the treatment upcoming literature. The very basics and traditional concepts
regimen may change. It led to the hypothesis that during of oncogenes have been outlined in this communication.
progression of the tumor, the cells acquire additional genetic Interested readers may further build their knowledge by
alterations which lead to formations of subclones of tumor reading more specialized literature.
cells [3, 4]. The traditional concept was that the initial genetic
alteration may affect a normal cell which is already References
differentiated, while the recent concept indicates that stem
1. Kumar V, Abbas AK, Aster JC. Neoplasia. In: Kumar V,
cell or progenitor cells are the first target [6]. Most
Abbas AK, Aster JC, editors. Robbins and Cotran
hematopoietic tumors and soft tissue sarcomas are initiated
Pathologic Basis of Disease. 9th ed. Philadelphia: Elsevier;
by activation of an oncogene, followed by alteration in tumor
2010. pp. 265-340.
suppressor genes and other oncogenes. In contrast, most
2. Walter JB, Talbot IS. The etiology and incidence of
carcinomas are initiated by loss of function of tumor
tumors. In: Walter JB, Talbot IS, editors. Walter and Israel
suppressor genes followed by alterations in oncogenes and
General Pathology. 7thed. New Delhi: Churchill
additional tumor suppressor genes [4].
Livngstone; 2015. pp. 503-34.
Significance of oncoproteins includes diagnosis and
3. Pierotti MA, Sozzi G, Croce CM. Mechanisms of oncogene
assessment of prognosis of different types of tumors as well
activation. In: Kufe DW, Pollock RE, Weichselbaum RR, et
as in therapeutics. Some of the drugs, its targets and uses are
al., editors. Holland-Frei Cancer Medicine. 6th edition.
depicted in table 2 [4].
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JBS 2016;3(4):35-37
Journal of Biomedical Sciences Oncogenes – the basics
Hamilton (ON): BC Decker; 2003. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK12538/
4. Croce CM. Oncogenes and cancer. N Engl J Med. 2008
Jan 31;358(5):502-11.
5. King MW. Classifications of Proto-Oncogenes. Available
online:
https://themedicalbiochemistrypage.org/oncogene.php
#classes. Accessed on 16.10.2017
6. Vicente-Dueñas C, Romero-Camarero I, Cobaleda C,
Sánchez-García I. Function of oncogenes in cancer
development: a changing paradigm. EMBO J. 2013 May
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