Cannella Sonia, Santoro Alessandra, Bruno Giuseppa, Pillon Marta, Mussolin Lara, Mangili Giovanna, Rosolen Angelo, Aricò Maurizio
Pediatric Hematology Oncology, Ospedale dei Bambini G. Di Cristina, Palermo, Italy.
Cancer. 2007 Jun 15;109(12):2566-71. doi: 10.1002/cncr.22718.
Monoallelic and biallelic mutations of the PRF1 gene have been reported in some cases of childhood lymphoma. Anaplastic large cell lymphoma (ALCL) accounts for 10% to 15% of all childhood lymphomas. To assess the possible role of PRF1 mutations in ALCL, the authors screened a series of patients collected by the Associazione Italiana di Ematologia Oncologia Pediatrica (AIEOP).
The authors investigated 44 patients with ALCL by direct sequence of the PRF1 gene. To address the issue of the prevalence of the most frequently observed PRF1 mutations in the control population, the authors examined a series of 400 healthy white control subjects for the 272C>T mutation (A91V).
A total of 6 different mutations were identified in 12 patients (27.3%). Eleven patients had 1 mutation whereas 1 patient was found to have 2 mutations. Of the 6 PRF1 mutations identified, 2 were novel mutations: 529C>T (resulting in R177C) and 1471G>A (resulting in D491N). The remaining 4 mutations were previously described; in particular, the 272C>T mutation (resulting in the A91V amino acid change) was found in 8 patients, whereas the 368G>A (R123H), 695G>A (R232H), and 1262T>G (F421C) mutations were all found in 1 case each. Overall, the incidence of PRF1 mutations was found to be significantly higher in patients with ALCL compared with 400 control subjects, among whom only heterozygous A91V was observed in 41 subjects (10.2%) (chi-square test, 10.9; P <.01).
Patients with childhood ALCL have a higher probability of being a carrier of a PRF1 mutation compared with healthy controls, suggesting a possible predisposing role.
在一些儿童淋巴瘤病例中已报道了PRF1基因的单等位基因和双等位基因突变。间变性大细胞淋巴瘤（ALCL）占所有儿童淋巴瘤的10%至15%。为评估PRF1突变在ALCL中的可能作用，作者筛选了意大利儿科血液肿瘤学协会（AIEOP）收集的一系列患者。
作者通过PRF1基因直接测序研究了44例ALCL患者。为解决对照人群中最常观察到的PRF1突变的患病率问题，作者检查了400名健康白人对照受试者是否存在272C>T突变（A91V）。
在12例患者（27.3%）中总共鉴定出6种不同突变。11例患者有1种突变，而1例患者有2种突变。在鉴定出的6种PRF1突变中，2种是新突变：529C>T（导致R177C）和1471G>A（导致D491N）。其余4种突变先前已有描述；特别是，8例患者中发现了272C>T突变（导致A91V氨基酸改变），而368G>A（R123H）、695G>A（R232H）和1262T>G（F421C）突变各在1例中发现。总体而言，发现ALCL患者中PRF1突变的发生率显著高于400名对照受试者，其中仅在41名受试者（10.2%）中观察到杂合A91V（卡方检验，10.9；P<.01）。
与健康对照相比，儿童ALCL患者携带PRF1突变的可能性更高，提示可能存在易感作用。
