- 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
The study, published in Nature, was a comprehensive analysis of genomes conducted on 178 primary cervical cancers and found that
- 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.
Cervical CancerCervical cancer 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 adenocarcinomas
- 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
- Worldwide, 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
Similarity with Endometrial CancerA significant finding in this study was that there were 8 cervical cancers which showed molecular similarity with endometrial cancer. These were characterized by
- Increased frequency of mutation in KRAS, PTEN and ARID1A genes
- Being mostly HPV-negative
ImmunotherapiesThe research team tried to identify genes that were over expressed in order to predict the response to immunotherapies. They found that the following genes were amplified:
- CD274 that codes for the PD-L1 immune checkpoint protein
- PDCD1LG2 that codes for the PD-L2 immune checkpoint protein
Novel mutations that were identified during the study include
Potential Therapeutic TargetDuring 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.
Signaling PathwaysThe 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 pathways
- Cervical Cancer Overview - (http://www.nccc-online.org/hpvcervical-cancer/cervical-cancer-overview/)