Part one of a series on DNA damage and cancer from Amelia Technologies

If you found out you had an eighty seven percent chance of developing breast cancer, what might you do? In acclaimed actress Angelina Jolie’s case, she took extreme preventative measures and got a double mastectomy. Jolie did this after test results revealed she had inherited a damaged, or mutated, version of the BRCA1 gene. BRCA1 and BRCA2 are genes involved in tumor suppression and DNA repair when normally functioning. DNA repair genes are some of the most critical; as their normal function is to detect and repair DNA mutations, when they themselves are damaged, genetic mutations persist and can result in that uncontrollable growth. Thus, the damage of DNA repair genes increases a person’s risk for cancer. Imagine them like soldiers; when they are wounded, the enemy has a higher chance of invading.

 

 

Cancer is an umbrella term for a group of diseases characterized by the uncontrolled growth and spread of abnormal cells due to mutation.

 

 

 

Cancer occurs when DNA is damaged, but the damage is not corrected properly, thus leading to a persisting mutation in the genome.

 

 

 

 

It is important to remember, that cancer is NOT triggered by a single mutation later in life.

 

 

 

Rather, in order to become completely tumorigenic, cancerous cells must go through stages from initiation, promotion and finally progression. Through each advance, the cancer accumulates additional mutations.

 

 

There are two major sources of mutation: Germline (as mentioned above) and Acquired.

Acquired mutations occur in the cells during the organism’s lifetime. The load of these mutations can be exacerbated by mutagenic (causing mutation) activities such as smoking, sunbathing and exposure to pollution.

 

Germline mutations, like the BRCA gene mutations, are less common but offer greater insight in cancer progression. A germline mutation occurs in a sperm cell or egg cell. Because the mutation affects reproductive cells, it can pass from generation to generation. Cancer caused by germline mutations is called inherited cancer. It accounts for about 5% to 20% of all cancers.

 

 

 

 

Germline mutations that occur in DNA repair genes, result in cancer predisposition disorders & syndromes. These can lead to an extreme increased incidence of cancers. For example, when the DNA repair systems that function to detect mis-matched nucleotides are damaged, this results in Lynch syndrome, a predisposition syndrome to early onset colorectal cancer (CRC). Familial Lynch syndrome accounts for between 1-5% of all CRC cases.

Another example is the damage of DNA repair systems that detect covalent modifications in the DNA due to UV exposure. This damage can result in Xeroderma pigmentosum or often erroneously called, “Vampire Syndrome”. This syndrome results in patients becoming extremely sensitive to UV rays and increases the risk of cancer 10-1000 fold.

Read more about a young patient afflicted with XP
here: https://www.bbc.co.uk/newsround/47667822

At Amelia Technologies, we develop state of the art technologies that both quantify this DNA damage and provide insight into therapeutics for the resulting disorders that occur because of this damage.

Stay tuned for the second part of this series, where we dive into the DNA  Repair “double edged sword”: How we can go about targeting DNA repair in cancer to treat it, and how current forms of chemotherapy can actually induce more DNA damage .