Selkirk Christina G, Vogel Kristen J, Newlin Anna C, Weissman Scott M, Weiss Shelly M, Wang Chi-Hsiung, Hulick Peter J
Center for Medical Genetics, NorthShore University HealthSystem, Evanston, IL, USA.
Fam Cancer. 2014 Dec;13(4):527-36. doi: 10.1007/s10689-014-9741-4.
Next-generation sequencing genetic testing panels for cancer susceptibility (cancer panels) have recently become clinically available. At present, clinical utility is unknown and there are no set criteria or guidelines established for whom to offer such testing. Although it may be a cost-effective method to test multiple cancer susceptibility genes concurrently, the rate of finding variants of unknown significance (VUS) may be high and testing may yield mutations in genes with no established management recommendations. We describe our Center's experience over a 14-month period (April 2012-June 2013) for patient interest and uptake in cancer panel testing and whether there were predictors of pursuing testing or identifying mutations. Using a clinical ranking system, patients' family histories were ranked from 0 to 3 (low likelihood to high likelihood for underlying genetic susceptibility). The clinical ranking system was assessed to determine its predictability of finding mutations. Of the 689 patients who met inclusion criteria, the option of pursuing a cancer panel was discussed with 357 patients; 63 (17.6 %) patients pursued testing. Those who pursued testing were more likely to be older, male, affected with cancer, affected with multiple primary cancers, and had a higher clinical rank than non-pursuers. There were no significant predictors of finding a mutation on panel testing. Of the 61 patients who have received results, there was a 6.6 % mutation rate and 19.7 % VUS rate. The yield of cancer panels in clinical practice is low and the strength of family history alone may not predict likelihood of finding a mutation.
用于癌症易感性检测的新一代测序基因检测板(癌症检测板)最近已在临床上可用。目前,其临床效用尚不清楚,并且对于哪些人应进行此类检测,尚未制定既定标准或指南。尽管同时检测多个癌症易感基因可能是一种具有成本效益的方法,但发现意义未明变异(VUS)的比率可能很高,并且检测可能会在没有既定管理建议的基因中产生突变。我们描述了我们中心在14个月期间(2012年4月至2013年6月)患者对癌症检测板检测的兴趣和接受情况,以及是否存在进行检测或识别突变的预测因素。使用临床分级系统,将患者的家族史从0到3进行分级(潜在遗传易感性的可能性从低到高)。对临床分级系统进行评估以确定其发现突变的可预测性。在符合纳入标准的689名患者中,与357名患者讨论了进行癌症检测板检测的选择;63名(17.6%)患者进行了检测。进行检测的患者比未进行检测的患者更可能年龄较大、为男性、患有癌症、患有多种原发性癌症,并且临床分级更高。在检测板检测中发现突变没有显著的预测因素。在已收到结果的61名患者中,突变率为6.6%,VUS率为19.7%。癌症检测板在临床实践中的检出率较低,仅家族史的强度可能无法预测发现突变的可能性。