1. In 1995 scientists from the National Institutes of Health (NHI) discovered that a
certain alteration in the breast cancer gene called BRCA1 was present in 1% of the
general Jewish population. BRCA1 is a tumor suppressor gene that usually have the
job of controlling cell growth and cell death. Both copies of a tumor suppressor gene
must be altered or mutated before a person will develop cancer. specific recurring
mutations have been found in individuals of Ashkenazi Jewish descent, and persons
from the Netherlands, Iceland, and Sweden. Mutations recur in these groups
because of a founder’s effect. "Founders" are a small group of people who, due to
geographic or religious isolation, interbred. When a small group of people
interbreeds over generations, specific rare mutations can recur and become more
common in the population. This is called a founder’s effect. Family history is the
strongest single predictor of a woman's chance of developing breast cancer. The first,
BRCA1 (for BReast CAncer gene), was discovered in 1994. Of the more than 100
alterations identified in each gene (BRCA1 and BRCA2) in families with hereditary breast
cancer, a few are found in subgroups of the general population. Three alterations were
initially identified in Ashkenazi families with hereditary breast cancer and later were found
in an unusually high percentage of the general Jewish population. In the United States,
between one in 400 and one in 800 people in the general population have a
BRCA1/2mutation. 20-30% of women diagnosed with breast cancer have members
of their family who have also been diagnosed. The oldest description of cancer
(although the word cancer was not used) was discovered in Egypt and dates back to
about 3000 BC. It is called the Edwin Smith Papyrus and is a copy of part of an
ancient Egyptian textbook on trauma surgery. It describes 8 cases of tumors or
ulcers of the breast that were treated by cauterization with a tool called the fire
drill. The writing says about the disease, “There is no treatment.”
2. In August 2013, Professor Alan Ashworth, builds on the old drug, Olaparib, into
drugs called PARP inhibitors. Professor Jorge Reis-Filho and his team fully
sequenced two tumors of patients with a faulty BRCA1 gene. Surprisingly, changes
in the genetic code of the two tumors looked almost entirely different from one
another. This information can now help scientists identify better treatment
strategies for patients with a faulty BRCA1 gene.
3. An enzyme called DNA gyrase makes a nick in the double helix and each side
separates. An enzyme called helicase unwinds the double-stranded DNA. Several
small proteins called single strand binding proteins (SSB) temporarily bind to each
side and keep them separated. An enzyme complex called DNA polymerase moves
down the DNA strands and adds new nucleotides to each strand. The nucleotides
pair with the complementary nucleotides on the existing stand (A with T, G with C).
A subunit of the DNA polymerase proofreads the new DNA. An enzyme called DNA
ligase seals up the fragments into one long continuous strand. The new copies
automatically wind up again.
4. Most oncogenes are mutations of certain normal genes called proto-oncogenes.
When a proto-oncogene mutates (changes) into an oncogene that can become
permanently turned on or activated when it is not supposed to be. When this
happens, the cell grows out of control, which can lead to cancer. A few cancer
syndromes are caused by inherited mutations of proto-oncogenes that cause the
oncogene to be turned on (activated). Multiple endocrine neoplasia type 2 (MEN2) is
caused by an inherited mutation in the gene called RET. People affected by this
syndrome often develop an uncommon thyroid cancer called medullary cancer of
the thyroid. They also develop other tumors, including pheochromocytoma and
nerve tumors. Most cancer-causing mutations involving oncogenes are acquired, not
inherited. They generally activate oncogenes by chromosome rearrangements, gene
duplication, or mutation. When tumor suppressor genes don't work properly, cells
can grow out of control, which can lead to cancer. Many different tumor suppressor
genes have been found. An important difference between oncogenes and tumor
suppressor genes is that oncogenes result from the activation(turning on) of protooncogenes, but tumor suppressor genes cause cancer when they are inactivated
(turned off). Inherited abnormalities of tumor suppressor genes have been found in
some family cancer syndromes. They cause certain types of cancer to run in
families.
5. Definition: A tumor suppressor gene that is associated with the development of
various cancers, especially breast and ovarian cancer , when inherited in a mutated
state. Inheriting a mutant copy of BRCA1 goes together with an 80% lifetime risk of
developing familial breast and ovarian cancer. It is uncalled for why mutations in a
gene that is essential for DNA damage repair in all cells would be in correlation with
the predisposition to only breast and ovarian cancers rather than an increased likely
hood to get all types of cancer. BRCA1 is located on chromosome 17. Breast
neoplasms can be identified by their histologic pattern. BRCA1 mutations are
mostly missense that happen over a long period of time or could happen
spontaneously.