- Centromere gene
expression score (CED) identified as key biomarker for cancer.
- High CES signals
- High level of
chromosome instability leads to better response to adjuvant therapy
Researchers from The Lawrence Berkeley National Laboratory's
Department of Energy have found clues to using genetic biomarkers to study the
need for adjuvant therapy like chemotherapy or radiotherapy in the treatment of
cancer. This is meant to allay fears associated with excessive treatment meted
out to cancer patients.
Scoring System for
The University of
Berkeley researchers found 14 genes that were over expressed in various types
of cancer and they developed a scoring system that could identify the prognosis of
cancer. The scoring system that these researchers developed aided in
identifying these two factors
- In some forms of cancer like in lung
cancer or breast cancer, a high score could signify poor prognosis.
- The scoring system could be used to accurately determine the response of patients to cancer treatments.
The necessity to develop
diagnostic methods to discern the need for cancer treatments stems from the use of chemotherapy
even in early stage lung cancer where
the effectiveness of the treatment is merely 10% but the patient could be
weighed down by the side effects of treatment.
‘High level of chromosome instability will lead to better response to adjuvant therapy in cancer patients.’
The study's principal
investigator who is a researcher with The University of Berkeley's Department
of Molecular and Cell Biology and department of Biological Systems and
Engineering, Dr. Gary Karpen said "The history of cancer treatment is filled
with overreaction. It is part of the ethics of cancer treatment to err on the
side of overtreatment, but these treatments have serious side effects
associated with them. For some people, it may be causing more trouble than if
the growth was left untreated."
Side Effects of
Cancer cells are
essentially the body's own cells, which is why the body's immune system is
unable to fight against the cancer cells. In chemotherapy, growing, active
cells are targeted in a bid to kill all cancer cells. As a result, other active
and growing cells of the body are also killed which include cells in the blood,
mouth and hair follicles.
The patients could
- Lowered immunity
- Numbness or weakness in the leg
- Sores in the mouth
- Nervous problems that could result in an inability to walk properly or feeling of being disoriented.
- Loss of memory
The extent of side
effects depends on the duration of chemotherapy, the health of the individual
and the drugs used for chemotherapy.
Side Effects of
is the use of
radiation to kill possible cancer cells at the site of cancer development. The
extent and type of side effects depend on the site of cancer and the health of
- Stiffness of the jaw
- Shortness of breath
Dr. Anshu Jain who is an
oncologist at Ashland Bellefonte Cancer Center and is the co-author of the
study said that the discovery of these biomarkers
was "very exciting" and that the "The biomarker score
provides predictive and prognostic information separate from and independent of
clinical and pathologic tumor characteristics that oncologists have available
today and which often provide only limited clinical value."
Genes that Regulate
Centromere and Kinetochores
The team of Berkeley
University researchers found a particular centromere protein was over expressed
in fruit flies which led to additional attachment sites. The significance of
studying these additional centromeres is given by Dr. Karpen "This
essentially makes new centromeres functional at more than one place on the
chromosome, and this is a huge problem because the spindle tries to connect to
all the sites. If you have two or more of these sites on the chromosome, the
spindles are pulling in too many directions, and you end up breaking the
chromosome during cell division. So over expression of these genes may be a
major contributing factor to chromosomal instability, which is a hallmark of
Role of Centromeres in
Though the presence of a large amount of
chromosome instability in cancers is well known, the effect of centromeres in
chromosome instability has never been studied. The researchers accessed
information from The Broad Institute, National Center for Biotechnology
Information and other institutions and analyzed data from thousands of human
tumors from more than 12 types of cancers. The researchers studied 31 genes for
their role in tumorigenesis.
- 14 genes were over expressed consistently in cancers.
- The kinetochore gene expression score strongly correlated with whether the patient survived after 5 years.
- The presence of a high number of these genes indicated that the patient would respond better to chemotherapy and radiotherapy.
- With respect to chromosome instability
- Presence of low to medium level of chromosome instability could make the cancer thrive.
- High level of instability makes the cancer cells more susceptible to cancer treatment.
kinetochore gene expression score (CES) will have a significant impact on
doctor recommendation for chemotherapy and radiation for cancer patients. In
future, after detailed studies, it could be used to determine the course of
treatment. The researchers were unable to find a correlation between high
chromosome instability and improvement in patient survival without any adjuvant therapy.
There are a number of
studies that are carried out to improve treatment options for cancer and to understand the
mechanism of cancer development. The presence of a set of guidelines
or a benchmark using the CES could soon save some cancer patients from
unnecessary adjuvant treatment which give rise to side effects.
- Side Effects of Chemotherapy - (http://www.cancer.net/navigating-cancer-care/how-cancer-treated/chemotherapy/side-effects-chemotherapy)
- Radiotherapy side effects - (http://www.cancerresearchuk.org/about-cancer/cancers-in-general/treatment/radiotherapy/side-effects/)