Please use this identifier to cite or link to this item: https://observatorio.fm.usp.br/handle/OPI/2056
Title: Evaluation of DNA from the Papanicolaou Test to Detect Ovarian and Endometrial Cancers
Authors: KINDE, IsaacBETTEGOWDA, ChetanWANG, YuxuanWU, JianAGRAWAL, NishantSHIH, Ie-MingKURMAN, RobertDAO, FannyLEVINE, Douglas A.GIUNTOLI, RobertRODEN, RichardESHLEMAN, James R.CARVALHO, Jesus PaulaMARIE, Suely Kazue NagahashiPAPADOPOULOS, NickolasKINZLER, Kenneth W.VOGELSTEIN, BertDIAZ JR., Luis A.
Citation: SCIENCE TRANSLATIONAL MEDICINE, v.5, n.167, article ID 167ra4, 10p, 2013
Abstract: Papanicolaou (Pap) smears have revolutionized the management of patients with cervical cancers by permitting the detection of early, surgically curable tumors and their precursors. In recent years, the traditional Pap smear has been replaced by a liquid-based method, which allows not only cytologic evaluation but also collection of DNA for detection of human papillomavirus, the causative agent of cervical cancer. We reasoned that this routinely collected DNA could be exploited to detect somatic mutations present in rare tumor cells that accumulate in the cervix once shed from endometrial or ovarian cancers. A panel of genes that are commonly mutated in endometrial and ovarian cancers was assembled with new whole-exome sequencing data from 22 endometrial cancers and previously published data on other tumor types. We used this panel to search for mutations in 24 endometrial and 22 ovarian cancers and identified mutations in all 46 samples. With a sensitive massively parallel sequencing method, we were able to identify the same mutations in the DNA from liquid Pap smear specimens in 100% of endometrial cancers (24 of 24) and in 41% of ovarian cancers (9 of 22). Prompted by these findings, we developed a sequence-based method to query mutations in 12 genes in a single liquid Pap smear specimen without previous knowledge of the tumor's genotype. When applied to 14 samples selected from the positive cases described above, the expected tumor-specific mutations were identified. These results demonstrate that DNA from most endometrial and a fraction of ovarian cancers can be detected in a standard liquid-based Pap smear specimen obtained during routine pelvic examination. Although improvements need to be made before applying this test in a routine clinical manner, it represents a promising step toward a broadly applicable screening methodology for the early detection of gynecologic malignancies.
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