先前的研究报道,与成人相比,小儿甲状腺乳头状癌(PTC)的临床表现和结局存在显着差异。先前的研究表明,儿童和成人PTC之间观察到的临床病理差异可能是由于存在不同的遗传改变。然而,对儿科PTCs中遗传事件的了解主要基于对辐射暴露的PTCs的研究或少数主要纳入青少年患者的研究.这项研究的目的是表征在一组主要是散发性儿科PTC患者中,在成人和辐射暴露的PTC中发现的MAPK途径的已知致癌改变。
筛选了35个儿科PTC中最常见的融合(RET/PTC1,RET/PTC2,RET/PTC3,ETV6-NTRK3和AGK-BRAF)和点突变(BRAFV600E和NRASQ61)。突变状态与临床病理数据相关。
在35例(57%)PTC病例中发现了20例突变。融合癌基因是发现的主要遗传改变。RET/PTC1-3重排发现13例(37%),3中的ETV6-NTRK3(9%),AGK-BRAF在4(11%),和BRAFV600E在3(9%)。在NRASQ61中未发现突变。BRAFV600E与年龄较大、肿瘤体积较大有关(p<0.05),RET/PTC3与较大的肿瘤大小和多灶性相关(p<0.05)。
该队列中的遗传特征与成年人中观察到的明显不同。尽管在较低的患病率下观察到,突变谱与接受辐射的儿科PTC中描述的非常相似.由于突变在超过40%的PTC病例中无法识别,在这些患者中进行的更全面的研究将有助于破译散发性儿科PTC的遗传格局.
Previous studies reported significant differences in the clinical presentation and outcomes of papillary thyroid carcinoma (PTC) in pediatric patients compared with adults. Previous studies have suggested that the clinicopathological differences observed between pediatric and adult PTCs may be due the existence of distinct genetic alterations. However, the knowledge of genetic events in pediatric PTCs is based primarily on studies in radiation-exposed PTCs or in the few studies that enrolled predominantly adolescent patients. The aim of this study was to characterize the known oncogenic alterations of the MAPK pathway found in adult and radiation-exposed PTCs in a cohort of predominantly sporadic pediatric PTC patients.
Thirty-five pediatric PTCs were screened for the most prevalent fusions (RET/PTC1, RET/PTC2, RET/PTC3, ETV6-NTRK3, and AGK-BRAF) and point mutations (BRAFV600E and NRASQ61) described in sporadic pediatric PTCs. The mutational status was correlated with clinicopathological data.
Mutations were found in 20 out of 35 (57%) PTC cases. Fusion oncogenes were the main genetic alterations found. RET/PTC1-3 rearrangements were found in 13 (37%), ETV6-NTRK3 in 3 (9%), AGK-BRAF in 4 (11%), and BRAFV600E in 3 (9%). No mutation was found in NRASQ61. BRAFV600E was associated with older age and larger tumor size (p < 0.05), and RET/PTC3 was associated with a larger tumor size and multifocality (p < 0.05).
The genetic signature in this cohort was remarkably different than that observed in adults. Although observed at a lower prevalence, the spectrum of mutations was quite similar to that described in radiation-exposed pediatric PTCs. As mutations were unidentifiable in over 40% of the PTC cases, more comprehensive studies conducted in these patients will help to decipher the genetic landscape of sporadic pediatric PTCs.