Hembree Timothy N, Teer Jamie K, Hakam Ardeshir, Chiappori Alberto A
Department of Thoracic Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA.
Cancer Control. 2016 Jan;23(1):61-6. doi: 10.1177/107327481602300111.
Uterine carcinosarcoma, a rare gynecological malignancy, often presents at the advanced stage with a poor prognosis because current therapies have not improved rates of survival. Genetic characterization of this tumor may lead to novel, specifically targeted drug targets to provide better treatment options for patients with this malignancy.
We present a case of a woman aged 61 years with uterine carcinosarcoma and retrospectively analyzed 100 study patients with uterine carcinosarcoma. From this group, 9 study patients underwent targeted sequencing of 1,321 genes.
All 9 study patients had at least 1 mutation in JAK2, KRAS, PIK3CA, CTNNB1, PTEN, FBXW7, TP53, and ERBB2; of these, TP53 was the most frequently mutated gene (6/9). In addition, ARID1A and KMT2C, which have been described and identified as part of a set of chromatin-remodeling genes, were also found in our analyses. From our 100-person cohort clinical analyses, study patients with stage 1 cancer had a median survival rate of 33 months (95% confidence interval, 19-109) compared with a median survival rate of 6 months (95% confidence interval, 3-12) in those with stage 4 disease.
Disease stage alone predicted the rate of clinical survival. Up to 50% in the study group were identified at having early stage disease (stage 1/2), indicating improved rates of overall detection compared with previously reported data. Our mutational analysis findings add to the number of tumors in which these mutations have been found and suggest that chromatin-remodeling dysregulation may play a role in the tumorigenesis of carcinosarcoma.
子宫癌肉瘤是一种罕见的妇科恶性肿瘤，由于目前的治疗方法未能提高生存率，其通常在晚期出现，预后较差。对这种肿瘤进行基因特征分析可能会带来新的、特异性靶向药物靶点，从而为患有这种恶性肿瘤的患者提供更好的治疗选择。
我们报告了一例61岁患有子宫癌肉瘤的女性病例，并对100例子宫癌肉瘤研究患者进行了回顾性分析。在该组中，9例研究患者接受了1321个基因的靶向测序。
所有9例研究患者在JAK2、KRAS、PIK3CA、CTNNB1、PTEN、FBXW7、TP53和ERBB2中至少有1个突变；其中，TP53是最常发生突变的基因（6/9）。此外，在我们的分析中还发现了ARID1A和KMT2C，它们已被描述并确定为一组染色质重塑基因的一部分。从我们100人的队列临床分析来看，1期癌症的研究患者中位生存率为33个月（95%置信区间，19 - 109），而4期疾病患者的中位生存率为6个月（95%置信区间，3 - 12）。
仅疾病分期就能预测临床生存率。研究组中高达50%的患者被确定为早期疾病（1/2期），这表明与先前报告的数据相比，总体检测率有所提高。我们的突变分析结果增加了发现这些突变的肿瘤数量，并表明染色质重塑失调可能在癌肉瘤的肿瘤发生中起作用。
