Knudson's heredity "2 hit cancers" involves the mutation driven cancers found in some childhood cancers.
In 1927 Muller proved that radiation makes mutations in fruit fly DNA thus connecting the cancer caused by radiation directly to the mutations occurring in the DNA.
https://en.wikipedia.org/wiki/Hermann_Joseph_Muller
In 1934 Muller suggested that one mutation was not enough since cancer did not immediately occur at the time of the mutation. The question was then how many mutations does it take?
In 1971 Knudson found the answer studying cancers in children In Retinalblastoma cancer could be caused by mutating both RB alleles. The smallest number of mutations possible to cause cancer was 2. Hence his "2 hit model"
In order for cancer to occur the genes mutated must be monumentally significant in the process of cancer and embryogenesis. Mutational childhood cancer is not how much DNA damage rather did the critical genes get damaged.
The retinalblastoma gene encodes a protein that suppresses cell cycles. (called a tumor suppressor but think in terms of embryogenesis where this protein stops the divisions)
https://en.wikipedia.org/wiki/Retinoblastoma_protein
RB is the lynch pin stopping cells from dividing.
Cancer is the division of cells without control.
Not the accumulations of mutations in DNA over a lifetime until some DNA damage level is reached.
Heredity and childhood cancer will reveal the small group of key genes involved in cancer through mutation and these damaged genes are all participants of cell division.
Most cancers are more complex. Most cancers will not be mutation triggered. Most cancers will begin through Co-carcinogenesis. Then the heredity of cell cycle mutations favor the continued life of these cancer cells.
Co-carcinogenesis is when a carcinogen interacts with a virus to cause cancer. The host's cell cycle divisions are turned on as if in embryogenesis. Further it is during these massive divisions that mutations can occur progressing the cancer. The virus and carcinogen are triggering the division of cells.
RB is the focus of nuclear viral oncoproteins.
http://www.nature.com/onc/journal/v25/n38/full/1209621a.html
Co-carcinogenesis
http://angelabiggs.blogspot.com/2017/04/co-carcinogenesis-emphasis-of-5-nuclear.html
Nuclear viruses turn on the high rate transcription involved with cell division. Which if they become inhibited by a carcinogen and their own polymerase can't use the freed system...cancer occurs.
Myc-c gene codes for a cell cycle transcription factor. Myc is expressed during the epiblast stage of embryogenesis.
https://www.nature.com/nature/journal/v500/n7460/full/nature12389.html
Myc-c favors a cell continuing to divide while low levels in the epiblast state dies. If the cell is cancerous with high myc it is favored to live.
Methylation occurs right before the Epiblast state. Methylation looks like it turns Myc on.
Myc-c is expressed in Burkitt lymphoma.
Epstein Barr virus has been linked to Burkitt lymphoma.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2095571/
Herpes viruses and retinoblastoma proteins
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2636798/
The EBV uses the estrogen receptors which trigger methylation. (the pathway is then magnified by the virus)
http://angelabiggs.blogspot.com/2017/05/virus-families-use-receptor-families.html
Which means the virus "awoke" more myc-c than is normally expressed through the receptor it used to infect
In 1927 Muller proved that radiation makes mutations in fruit fly DNA thus connecting the cancer caused by radiation directly to the mutations occurring in the DNA.
https://en.wikipedia.org/wiki/Hermann_Joseph_Muller
In 1934 Muller suggested that one mutation was not enough since cancer did not immediately occur at the time of the mutation. The question was then how many mutations does it take?
In 1971 Knudson found the answer studying cancers in children In Retinalblastoma cancer could be caused by mutating both RB alleles. The smallest number of mutations possible to cause cancer was 2. Hence his "2 hit model"
In order for cancer to occur the genes mutated must be monumentally significant in the process of cancer and embryogenesis. Mutational childhood cancer is not how much DNA damage rather did the critical genes get damaged.
The retinalblastoma gene encodes a protein that suppresses cell cycles. (called a tumor suppressor but think in terms of embryogenesis where this protein stops the divisions)
https://en.wikipedia.org/wiki/Retinoblastoma_protein
RB is the lynch pin stopping cells from dividing.
Cancer is the division of cells without control.
Not the accumulations of mutations in DNA over a lifetime until some DNA damage level is reached.
Heredity and childhood cancer will reveal the small group of key genes involved in cancer through mutation and these damaged genes are all participants of cell division.
Most cancers are more complex. Most cancers will not be mutation triggered. Most cancers will begin through Co-carcinogenesis. Then the heredity of cell cycle mutations favor the continued life of these cancer cells.
Co-carcinogenesis is when a carcinogen interacts with a virus to cause cancer. The host's cell cycle divisions are turned on as if in embryogenesis. Further it is during these massive divisions that mutations can occur progressing the cancer. The virus and carcinogen are triggering the division of cells.
RB is the focus of nuclear viral oncoproteins.
http://www.nature.com/onc/journal/v25/n38/full/1209621a.html
Co-carcinogenesis
http://angelabiggs.blogspot.com/2017/04/co-carcinogenesis-emphasis-of-5-nuclear.html
Nuclear viruses turn on the high rate transcription involved with cell division. Which if they become inhibited by a carcinogen and their own polymerase can't use the freed system...cancer occurs.
Myc-c gene codes for a cell cycle transcription factor. Myc is expressed during the epiblast stage of embryogenesis.
https://www.nature.com/nature/journal/v500/n7460/full/nature12389.html
Myc-c favors a cell continuing to divide while low levels in the epiblast state dies. If the cell is cancerous with high myc it is favored to live.
Methylation occurs right before the Epiblast state. Methylation looks like it turns Myc on.
Myc-c is expressed in Burkitt lymphoma.
Epstein Barr virus has been linked to Burkitt lymphoma.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2095571/
Herpes viruses and retinoblastoma proteins
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2636798/
The EBV uses the estrogen receptors which trigger methylation. (the pathway is then magnified by the virus)
http://angelabiggs.blogspot.com/2017/05/virus-families-use-receptor-families.html
Which means the virus "awoke" more myc-c than is normally expressed through the receptor it used to infect
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