Whole Exome Sequencing Sheds Light on Cervical Cancer

The cervix is lower part of the uterus and cervical cancer occurs in the cells of the cervix. In cervical cancer, the cells of the cervix grow abnormally and invade other tissues and organs of the body including lungs, liver, bladder, vagina, and rectum. All women are at risk for cervical cancer and occurs most often in women over age 30. What is the exact cause of the cancer? no one knows. Research suggests that the main cause of cervical cancer is the infection with certain types of human papillomavirus (HPV). HPV is a virus that is passed from one person to another during sex. When a person gets exposed to HPV, the immune system fights with the virus and kills it before it can do any harm. However, in some people the virus survives for years and causes cervical cells to become cancer cells. Early detected cervical cancer is treatable and associated with long survival rate. Cervical cancer is the fourth most common type of cancer for women worldwide. More than 13,000 women in the United States will be diagnosed with cervical cancer each year, and more than 4,000 of women will die. Pap tests can detect cervical precancer before it turns into cancer. Because many women getting regular Pap tests, the number of deaths from cervical cancer have decreased significantly. There are different treatment options and survival outcomes for cervical cancer patients with early versus advanced stage. Treatment may include surgery, radiation therapy, chemotherapy, or a combination. Despite advancement in technologies the prognosis of advanced/recurrent cervical cancer patients remains poor. The development of effective treatments for patients with  advanced/recurrent cervical cancer remains a medical need.


For cancer genomics, whole-exome sequencing (WES) plays a very important role for better understanding of the disease. It  involves sequencing and analysis of entire exomes of a cancer cell and comparing it to a patient's healthy cells. Exome is the protein-coding portions of the genome. Scientists look for mutations in the exome of tumor cell while comparing with the exome of healthy cells. It is possible to identify factors responsible for unwanted tumor growth by studying various mutations present in exome of cancer cell. A recent study, performed by researchers from Italy and the United States, describes the use of Whole Exome Sequenicng to further investigate potential treatment targets. Researchers performed exome sequencing on cervical cancer tumor, patient-derived cervical cancer cell line, and matched normal samples from 69 women with advanced or recurrent forms of the disease. They analyzed 54 fresh-frozen cervical carcinoma tumors and 15 primary cervical cancer cell lines, along with 56 matched-normal DNA. Most of the cervical cancer cases were positive for Human-Papillomavirus-type-16/18. The scientists used Illumina HiSeq Instruments to perform sequencing of protein-coding portions of the genome captured with a NimbleGen/Roche exome capture reagent. Exome analysis enabled researchers uncovered recurrent somatic missense mutations in 22 genes and identified12 copy number gains and 40 losses. The copy number changes and single nucleotide variants were associated with pathways involved in chormatin remodeling, cell cycle regulation, apoptosis, and signaling by ERBB2/PI3K/AKT/mTOR genes. Based on fully sequenced cell lines, xenografts and existing inhibitors/drugs studies, scientists suggest that a large subset of cervical tumors (>70%) might benefit from existing ERBB2/PIK3CA/AKT/mTOR-targeted drugs. Encouraging results of experiment with afatinib and neratinib, two USDA approved drugs in lung and breast cancer patients, may represent a potentially valid therapeutic options for patients harboring ERBB2-mutated advanced/recurrent cervical cancers."