Evaluation of DNA from the Papanicolaou test to detect ovarian and endometrial cancers.
Evaluation of DNA from the Papanicolaou test to detect ovarian and endometrial cancers.
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DOI：
10.1126/scitranslmed.3004952
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发表时间：
2013-01-09
影响因子：
17.1
通讯作者：
Diaz LA Jr
中科院分区：
文献类型：
--
作者：
Kinde I;Bettegowda C;Wang Y;Wu J;Agrawal N;Shih IeM;Kurman R;Dao F;Levine DA;Giuntoli R;Roden R;Eshleman JR;Carvalho JP;Marie SK;Papadopoulos N;Kinzler KW;Vogelstein B;Diaz LA Jr
巴氏涂片检查彻底改变了宫颈癌患者的治疗方法，可以检测出早期可手术治愈的肿瘤及其癌前病变。近年来，传统的巴氏涂片已被基于液体的方法所取代，该方法不仅可以进行细胞学评估，还可以收集DNA以检测人乳头瘤病毒（宫颈癌的病原体）。我们推断，这种常规收集的 DNA 可用于检测罕见肿瘤细胞中存在的体细胞突变，这些肿瘤细胞一旦因子宫内膜癌或卵巢癌脱落，就会在宫颈中积累。一组在子宫内膜癌和卵巢癌中常见突变的基因与来自 22 种子宫内膜癌的新全外显子组测序数据以及之前发表的其他肿瘤类型的数据进行了组装。我们使用该面板搜索 24 种子宫内膜癌和 22 种卵巢癌中的突变，并在所有 46 个样本中鉴定出突变。通过灵敏的大规模并行测序方法，我们能够从 100% 的子宫内膜癌（24 例中的 24 例）和 41% 的卵巢癌（22 例中的 9 例）的液体巴氏涂片样本中鉴定出相同的 DNA 突变。在这些发现的推动下，我们开发了一种基于序列的方法来查询单个液体巴氏涂片样本中 12 个基因的突变，而无需事先了解肿瘤的基因型。当应用于从上述阳性病例中选出的 14 个样本时，鉴定出了预期的肿瘤特异性突变。这些结果表明，大多数子宫内膜癌和一小部分卵巢癌的 DNA 可以在常规盆腔检查期间获得的标准液基巴氏涂片样本中检测到。尽管在以常规临床方式应用该测试之前还需要进行改进，但它代表了朝着广泛适用的妇科恶性肿瘤早期检测筛查方法迈出了有希望的一步。
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 In recent years, the traditional Pap smear has been replaced by a liquid-based method, which allows not only cytologic evaluation but also collection of DNA for detection of human papillomavirus, the causative agent of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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影响因子：
3.5
作者：
Barrow, E.;Robinson, L.;Evans, D. G.
通讯作者：
Evans, D. G.
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
14.9
作者：
Forbes SA;Bindal N;Bamford S;Cole C;Kok CY;Beare D;Jia M;Shepherd R;Leung K;Menzies A;Teague JW;Campbell PJ;Stratton MR;Futreal PA
通讯作者：
Futreal PA
影响因子：
7.2
作者：
DeSimone, Christopher P.;Day, Misty E.;Modesitt, Susan C.
通讯作者：
Modesitt, Susan C.
影响因子：
6.4
作者：
Bray, Freddie;Ren, Jian-Song;Ferlay, Jacques
通讯作者：
Ferlay, Jacques