Somatic Mutations: Primary cause of cancer, leading cells to grow uncontrollably.
Cancer Cells vs Normal Cells:
Normal cells grow only when signaled, stop growing when told, die when not needed, and stay in place.
Cancer cells ignore stop signals, often synthesize their own growth signals, steal blood supply, grow indefinitely, resist dying, and invade other tissues (metastasis).
Cancer Development
Begins with mutations in a single somatic cell.
Mutation leads to uncontrolled cell division and further mutations.
Tumor cells undergo a form of natural selection, favoring mutations that increase growth or drug resistance.
Genetic Structure of Tumors
Tumors have a complex web of mutations, often thousands.
Different mutations in different tumors and within different parts of the same tumor.
Higher mutation rates in cancer cells due to increased DNA damage and loss of replication control.
Mutation Effects
Cancer cells ignore regulatory checkpoints, leading to improper DNA replication and chromosomal anomalies.
Mutations can enhance growth or drug resistance.
Genetic Diversity in Tumors
Each tumor is unique with random genetic changes.
Difficult to predict mutation types and effects.
Tumors consist of genetically diverse cells, complicating treatment.
Study Example: Renal Cell Carcinoma
Tumor cells in the kidney metastasized to other parts.
Sequencing revealed numerous mutations: 101 non-synonymous point mutations and 32 INDELs.
Some mutations were common across samples, others unique to certain sectors or metastases.
Presence of tetraploid cells indicating major division errors.
Types of Genetic Changes Leading to Cancer
Mutations in genes stimulating growth (proto-oncogenes).
Mutations in genes suppressing growth (tumor suppressor genes).
Mutations affecting programmed cell death (apoptosis).
Dominance and Recessiveness in Mutations
Loss-of-function mutations in "stop" proteins are typically recessive.
Conclusion
Cancer is fundamentally a genetic disease caused by somatic mutations.
Somatic Mutations: Primary cause of cancer, leading cells to grow uncontrollably.
Cancer Cells vs Normal Cells:
Normal cells grow only when signaled, stop growing when told, die when not needed, and stay in place.
Cancer cells ignore stop signals, often synthesize their own growth signals, steal blood supply, grow indefinitely, resist dying, and invade other tissues (metastasis).
Cancer Development
Begins with mutations in a single somatic cell.
Mutation leads to uncontrolled cell division and further mutations.
Tumor cells undergo a form of natural selection, favoring mutations that increase growth or drug resistance.
Genetic Structure of Tumors
Tumors have a complex web of mutations, often thousands.
Different mutations in different tumors and within different parts of the same tumor.
Higher mutation rates in cancer cells due to increased DNA damage and loss of replication control.
Mutation Effects
Cancer cells ignore regulatory checkpoints, leading to improper DNA replication and chromosomal anomalies.
Mutations can enhance growth or drug resistance.
Genetic Diversity in Tumors
Each tumor is unique with random genetic changes.
Difficult to predict mutation types and effects.
Tumors consist of genetically diverse cells, complicating treatment.
Study Example: Renal Cell Carcinoma
Tumor cells in the kidney metastasized to other parts.
Sequencing revealed numerous mutations: 101 non-synonymous point mutations and 32 INDELs.
Some mutations were common across samples, others unique to certain sectors or metastases.
Presence of tetraploid cells indicating major division errors.
Types of Genetic Changes Leading to Cancer
Mutations in genes stimulating growth (proto-oncogenes).
Mutations in genes suppressing growth (tumor suppressor genes).
Mutations affecting programmed cell death (apoptosis).
Dominance and Recessiveness in Mutations
Loss-of-function mutations in "stop" proteins are typically recessive.
Conclusion
Cancer is fundamentally a genetic disease caused by somatic mutations.