- Scientists from
The Cancer Genome Atlas Research Network have identified alteration in the
genes and molecular signaling pathways in cervical cancer patients.
- 8 cervical cancer
patients who were HPV negative were found to have mutations in the genes
KRAS, PTEN and ARID1A.
- Some cancers were
found to be similar to endometrial cancers, highlighting that these
cancers could be caused due to genetic factors.
research team in the The Cancer Genome Atlas (TCGA) Research Network has found
novel molecular characteristics as well as genomic features of cervical cancer
which can be used for classification of the cancer. Such sub-classification
will aid in developing targeted therapies which could be more effective for the
study, published in Nature
, was a
comprehensive analysis of genomes conducted on 178 primary cervical cancers and
- More than 70 % of
the tumors had alterations in the genes.
- One or both of
the two important cell signaling pathways were affected.
- A subset of
tumors did not exhibit any sign of an infection by the human
papillomavirus (HPV) infection.
was a multilaboratory study with the involvement of scientists from National
Human Genome Research Institute (NHGRI), The National Cancer Institute (NCI)
and the National Institutes of Health (NIH).
is a cancer of the cervix,
which is the narrow opening
from the vagina into the uterus. The normal color of the cervix is a pink
color, covered with squamous cells
that are flat and thin. The cervical
canal is made up of columnar cells
while the area where these cells meet
is called the transformation zone
or the T-zone
. The T- zone is
the most common location for a cancer of the cervix.
- 80 to 90% are
squamous cell cancers
- 10 to 20% are
- In the U.S, over
12,000 women are diagnosed with cervical cancer each year
- 4,000 of women
die every year due to cervical cancer
500,000 new cases of cervical cancer are detected every year
- 250,000 deaths
occur each year worldwide due to this cancer
- Pap smear test is
used to detect cervical abnormalities early
cancer most often affects women who are middle aged, between 35-55 years of
age; it seldom occurs in women younger than 20 years of age.
Acting Director of The National Cancer Institute, Dr. Douglas Lowy, said that
the vast majority of cervical cancer incidences are due to persistent infection
with HPV that are oncogenic. There are effective vaccines which offer a means
of prevention against some of the most oncogenic types of HPV. However, the
only hitch to the vaccination program, according to the director, is that most
women who will develop this cancer over the next 2 years are beyond the age of
protection by the vaccine. Therefore, there is still an
urgent need to identify therapies that will prevent the development of this
type of cancer. This latest TCGA analysis is expected to improve efforts to
identify drugs which target important cervical cancer genomes along with the
Similarity with Endometrial Cancer
significant finding in this study was that there were 8 cervical cancers which
showed molecular similarity with endometrial cancer. These were characterized
frequency of mutation in KRAS, PTEN and ARID1A genes
- Being mostly
Jean-Claude Zenklusen, Director of the TCGA program office said that the
presence of endometrial like cervical cancers that were HPV negative showed
that not all cervical cancers were associated with an HPV infection. It showed
that a small percentage of these tumors could be solely associated with genetic
or other factors. The Director of the program, Dr. Jean, further stated that
this was one of the most important aspects of the TCGA program.
research team tried to identify genes that were over expressed in order to
predict the response to immunotherapies. They found that the following genes
- CD274 that codes
for the PD-L1 immune checkpoint protein
- PDCD1LG2 that
codes for the PD-L2 immune checkpoint protein
are several previous immunotherapeutic agents that have been found to be
effective against checkpoint inhibitors.
mutations that were identified during the study include
the study, there were several instances of cervical cancer where the BCAR4
genes were fused and resulted in a non-coding long RNA that was found to be
responsive to lapatinib
. This is a drug taken orally by breast cancer
patients as it inhibits an important pathway. This could be a potential drug
therapy for cervical cancer patients with this mutation.
study findings also revealed that nearly three fourths of the cervical cancer
cases were due to genetic alterations in either one or both the following
study provided many significant targets for cervical cancer therapy but the
scientists involved in the study were not able to determine if HPV positive
cervical cancer would respond to therapy similar to HPV negative cervical
cancer. A previous study showed that the presence of HPV antibodies in people
cancers was a marker of better prognosis. The new targets for
therapy identified by this study could, hopefully, aid in improving the
prognosis of patients without HPV antibodies too.
- Cervical Cancer Overview - (http://www.nccc-online.org/hpvcervical-cancer/cervical-cancer-overview/)