Genetic Mutations in Cancer

Study Notes

A deletion on chromosome 5 can fuse part of the ALK gene with part of another gene called EML4, creating a fusion gene in a subset of lung cancers.
HER2 amplification and overexpression in breast cancers can be treated with antibodies or drugs that block HER2 activity, leading to cessation of tumor growth and tumor regression.
RAS mutations are the most common type of abnormality involving proto-oncogenes in human tumors, occurring in 15-20% of cases.
RAS genes (HRAS, KRAS, NRAS) are commonly activated by point mutations, trapping RAS in its active state and forcing the cell into a continuously proliferating state.
Transcription factors like MYC can activate the transcription of other genes, and its amplification or translocation can contribute to cancer development.

Tumor suppressor genes apply brakes to cell proliferation, and their mutation can lead to uncontrolled cell growth.
The Retinoblastoma (RB) gene regulates the G1/S checkpoint and is located on chromosome 13.
Mutations in DNA repair genes can lead to an increase in mutations in other genes, including proto-oncogenes and tumor suppressor genes.

Gene amplification can increase the expression of oncogenes.
Deletions can lead to the loss of tumor suppressor genes.
Most human cancers have molecular defects that affect one or more components of growth factor signaling pathways.

Normal cells require stimulation by growth factors to proliferate, but cancer cells can acquire the ability to synthesize their own growth factors, creating an autocrine loop.
Oncogenes can encode growth factor receptors, such as receptor tyrosine kinases, which can be activated by point mutations, gene rearrangements, or gene amplifications.
Examples of growth factor receptors involved in cancer include ERBB1 (EGFR) and ERBB2 (HER2).

Retinoblastoma is a childhood tumor that can occur sporadically or be inherited as an autosomal dominant trait.
The two-hit hypothesis explains the development of retinoblastoma, requiring two mutations (hits) to inactivate both normal alleles of the RB locus.
TP53, located on chromosome 17p, is a tumor suppressor gene that is mutated in over 70% of human cancers and plays a crucial role in DNA repair, cell division, and cell death by apoptosis.

APC (Adenomatous polyposis coli) is a tumor suppressor gene that functions by downregulating growth-promoting signaling pathways and is associated with familial adenomatous polyposis.
APC loss of function can contribute to the development of colon cancer.
DNA repair genes ensure accurate copying of genetic information during cell division, and their mutation can lead to an increase in cancer-causing mutations.