The Familial Gastrointestinal Cancer Registry at Zane Cohen Centre for Digestive Diseases and Department of Surgery, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Pediatr Blood Cancer. 2012 Oct;59(4):652-6. doi: 10.1002/pbc.24019. Epub 2011 Dec 16.
Heterozygous germline mutations in DNA mismatch repair (MMR) genes cause Lynch syndrome. Biallelic MMR mutations cause a distinct syndrome characterized by brain tumors, lymphoid malignancies, and gastrointestinal cancers during childhood. These children usually succumb to multiple cancers before adulthood. We developed a surveillance protocol aiming at early detection for these individuals and report the 10-year experience with a kindred.
On the basis of genetic testing and early age tumors, the kindred started a cancer surveillance protocol based on the crude estimates of cancer risks and available cancer screening: imaging, endoscopy, and hematologic tests.
Over the 10-year follow-up period, the screening protocol detected 15 tumors. These included three high-grade adenomatous colonic polyps and two colon cancers. In one child, MRI revealed an asymptomatic anaplastic astrocytoma which was treated by complete resection and radiation. All three cancers identified during surveillance were small and asymptomatic at diagnosis. The two sisters are currently 16 and 18 years of age with no evidence of malignant disease. Both parents have annual colonoscopies and the father at 43 years had two colonic adenomatous polyps.
We report on the long-term outcome in patients with biallelic MMR mutations who benefited from prophylactic cancer surveillance. Genetic screening and subsequent surveillance led to earlier recognition of asymptomatic tumors at stages more amenable to resection and probable cure. Multicenter collaboration and implementation of surveillance guidelines is necessary to further determine genotype-phenotype correlations.
DNA 错配修复（MMR）基因的杂合胚系突变导致林奇综合征。双等位 MMR 突变导致一种独特的综合征，其特征是儿童期发生脑瘤、淋巴恶性肿瘤和胃肠道癌症。这些儿童通常在成年前死于多种癌症。我们制定了一项旨在早期发现这些个体的监测方案，并报告了一个家系的 10 年经验。
根据遗传测试和早期肿瘤，该家系根据癌症风险的粗略估计和可用的癌症筛查开始了癌症监测方案：影像学、内窥镜检查和血液学检查。
在 10 年的随访期间，筛查方案检测到 15 个肿瘤。其中包括三个高级别腺瘤性结肠息肉和两个结肠癌。在一名儿童中，MRI 显示出无症状的间变性星形细胞瘤，通过完全切除和放射治疗进行了治疗。在监测中发现的所有三种癌症在诊断时均较小且无症状。这两个姐妹目前分别为 16 岁和 18 岁，没有恶性疾病的证据。父母双方均每年进行结肠镜检查，43 岁的父亲有两个结肠腺瘤性息肉。
我们报告了受益于预防性癌症监测的双等位 MMR 突变患者的长期结果。遗传筛查和随后的监测导致了无症状肿瘤的早期识别，这些肿瘤处于更适合切除和可能治愈的阶段。需要多中心合作和实施监测指南，以进一步确定基因型-表型相关性。
