Kolialexi A, Mavrou A, Tsenghi C, Tsangaris G T, Dafermou E, Tzortzatou F, Polychronopoulou S, Haidas S, Metaxotou C
1st Department of Pediatrics, Athens University, Aghia Sophia Children's Hospital, Greece.
Anticancer Res. 1998 Jul-Aug;18(4A):2359-64.
In order to clarify the possible connection between autosomal folate sensitive Fragile Sites (FS) and genetic susceptibility to haemopoetic disease in children we investigated the frequency and distribution of FS in the Peripheral Blood Lymphocytes (PBL) of 56 children with newly diagnosed and untreated haematologic malignancies and their parents. The incidence was compared with that of 146 normal controls (children and adults). In all patients the Bone Marrow (BM) karyotype was also determined. Heritable FS were detected in 49 patients (87.5%). 20 children had more than one FS and in all cases it was inherited from one of their parents, although there was a significant excess of transmitting mothers. 19 different FS were identified: 14 common, 4 rare and one, 22q11, which has not been previously reported, but it is considered as important as it coincides with the cancer breakpoint resulting in the formation of the Philadelphia (Ph) chromosome. The frequency of FS in the PBL of the patients was significantly higher than in the controls and this increase was independent of any abnormality detected in the malignant cells of the BM. However, patients with an abnormal BM karyotype displayed increased frequency of FS induction as compared to patients with a normal karyotype. In three cases the heritable FS was found to be at or near the breakpoints of the chromosomal rearrangements detected in the malignant cells. The findings are discussed with regard to cancer specific breakpoints, oncogene loci and sites where viral DNA can be inserted to the genome. The results of this study suggest that autosomal folate sensitive FS may increase the risk for haematologic malignancies through a complex mechanism which remains to be clarified.
为了阐明常染色体叶酸敏感脆性位点（FS）与儿童血液系统疾病遗传易感性之间的可能联系，我们调查了56例新诊断且未经治疗的血液系统恶性肿瘤患儿及其父母外周血淋巴细胞（PBL）中FS的频率和分布。将该发病率与146名正常对照者（儿童和成人）进行比较。对所有患者还测定了骨髓（BM）核型。在49例患者（87.5%）中检测到可遗传的FS。20名儿童有不止一个FS，且在所有情况下均从其父母一方遗传而来，尽管传递FS的母亲明显过多。鉴定出19种不同的FS：14种常见的，4种罕见的，还有一种22q11，此前未见报道，但因其与导致费城（Ph）染色体形成的癌症断点重合而被认为很重要。患者PBL中FS的频率显著高于对照组，且这种增加与BM恶性细胞中检测到的任何异常无关。然而，与核型正常的患者相比，BM核型异常的患者FS诱导频率增加。在3例病例中，发现可遗传的FS位于恶性细胞中检测到的染色体重排断点处或附近。结合癌症特异性断点、癌基因位点以及病毒DNA可插入基因组的位点对这些发现进行了讨论。本研究结果表明，常染色体叶酸敏感FS可能通过一种尚待阐明的复杂机制增加血液系统恶性肿瘤的风险。
