Page 225 - Textbook of Pathology, 6th Edition

In cancer, the transformed cells are produced by 209
abnormal cell growth due to genetic damage to these normal
controlling genes. Thus, corresponding abnormalities in these
4 cell regulatory genes are as under:
i) Activation of growth-promoting oncogenes causing
transformation of cell (mutant form of normal proto-
oncogene in cancer is termed oncogene). Many of these cancer CHAPTER 8
associated genes, oncogenes, were first discovered in viruses,
and hence named as v-onc. Gene products of oncogenes are
called oncoproteins. Oncogenes are considered dominant since
they appear in spite of presence of normal proto-oncogenes.
ii) Inactivation of cancer-suppressor genes (i.e. inactivation of
anti-oncogenes) permitting the cellular proliferation of
transformed cells. Anti-oncogenes are active in recessive form Neoplasia
i.e. they are active only if both alleles are damaged.
iii) Abnormal apoptosis regulatory genes which may act as
oncogenes or anti-oncogenes. Accordingly, these genes may
be active in dominant or recessive form.
iv) Failure of DNA repair genes and thus inability to repair the
DNA damage resulting in mutations.

Cancer-related Genes and Cell Growth
(Hallmarks of Cancer)

It is apparent from the above discussion that genes control
the normal cellular growth, while in cancer these controlling
genes are altered, typically by mutations. A large number of
such cancer-associated genes have been described, each with
a specific function in cell growth. Some of these genes are
Figure 8.18 The monoclonal origin of tumour cells in uterine commonly associated in many tumours (e.g. p53 or TP53),
leiomyoma.
while others are specific to particular tumours. Therefore, it
is considered appropriate to discuss the role of cancer-related
Ultimately, the cells so formed are genetically and genes with regard to their functions in cellular growth.
phenotypically transformed cells having phenotypic features Following are the major genetic properties or hallmarks of cancer:
of malignancy—excessive growth, invasiveness and distant 1. Excessive and autonomous growth: Growth-promoting
metastasis. oncogenes.
2. Refractoriness to growth inhibition: Growth suppressing
4. Genetic theory of cancer. Cell growth of normal as well anti-oncogenes.
as abnormal types is under genetic control. In cancer, there 3. Escaping cell death by apoptosis: Genes regulating
are either genetic abnormalities in the cell, or there are normal apoptosis and cancer.
genes with abnormal expression. The abnormalities in genetic 4. Avoiding cellular aging: Telomeres and telomerase in
composition may be from inherited or induced mutations cancer.
(induced by etiologic carcinogenic agents namely: chemicals, 5. Continued perfusion of cancer: Cancer angiogenesis.
viruses, radiation). The mutated cells transmit their 6. Invasion and distant metastasis: Cancer dissemination.
characters to the next progeny of cells and result in cancer. 7. DNA damage and repair system: Mutator genes and

5. Genetic regulators of normal and abnormal mitosis. In cancer.
normal cell growth, regulatory genes control mitosis as well 8. Cancer progression and tumour heterogeneity: Clonal
as cell aging, terminating in cell death by apoptosis. aggressiveness.
9. Cancer a sequential multistep molecular phenomenon:
In normal cell growth, there are 4 regulatory genes: Multistep theory.
i) Proto-oncogenes are growth-promoting genes i.e. they 10. MicroRNAs in cancer: OncomiRs.
encode for cell proliferation pathway. These properties of cancer cells are described below in
ii) Anti-oncogenes are growth-inhibiting or growth suppressor terms of molecular genetics and schematically illustrated in
genes. Fig. 8.19.
iii) Apoptosis regulatory genes control the programmed cell
death. 1. EXCESSIVE AND AUTONOMOUS GROWTH:
iv) DNA repair genes are those normal genes which regulate GROWTH PROMOTING ONCOGENES
the repair of DNA damage that has occurred during mitosis Mutated form of normal protooncogenes in cancer is called
and also control the damage to proto-oncogenes and anti- oncogenes. Protooncogenes become activated oncogenes by
oncogenes. following mechanisms as under: