Sjursen Wenche, Hyldebrandt Hanne K, Lavik Liss Anne S, Haukanes Bjørn Ivar, Ariansen Sarah, Briskemyr Siri, Sylvander Anna E, Haavind Marianne T, Olsen Maren F, Røyset Elin S, Vetti Hildegunn, Stormorken Astrid, Grindedal Eli Marie
Department of Medical Genetics, St Olavs University Hospital, Trondheim, Norway.
Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Hered Cancer Clin Pract. 2024 Sep 27;22(1):20. doi: 10.1186/s13053-024-00292-6.
In Norway, we have offered testing of PMS2 since 2006, and have a large national cohort of carriers. The aim of this study was to describe all PMS2 variants identified, and to describe frequency, spectrum and penetrance of cancers in carriers of class 4/5 variants.
All detected PMS2 variants were collected from the diagnostic laboratories and reclassified according to ACMG criteria and gene specific guidelines. Data on variant, gender, cancer diagnosis, age at diagnosis, and age at last known follow-up was collected on all carriers of class 4/5 variants from electronic patient records. The Kaplan-Meier algorithm was used to calculate cumulative risk of any cancer, colorectal cancer and endometrial cancer.
In total, 220 different PMS2 variants were detected. Twenty nine class 4/5 variants were identified in 482 carriers. The most common pathogenic variant was the founder mutation c.989-1G > T, detected in 204 patients from 58 families. Eighty seven out of 482 (18.0%) had been diagnosed with colorectal cancer, 10 of these (11.8%) before 40 years. Cumulative risk at 70 years in our cohort was 34.7% for colorectal cancer and 26.1% for endometrial cancer.
After 15 years of genetic testing, 29 different class 4/5 variants have been detected in Norway. Almost half of Norwegian PMS2 carriers have the founder variant 989-1G > T. Penetrance of colorectal cancer in our cohort was moderate but variable, as 11.5% of those diagnosed were younger than 40 years.
自2006年起，挪威开始提供PMS2检测，拥有大量全国性的携带者队列。本研究的目的是描述所鉴定出的所有PMS2变异，并描述4/5类变异携带者中癌症的频率、谱型和外显率。
从诊断实验室收集所有检测到的PMS2变异，并根据美国医学遗传学与基因组学学会（ACMG）标准和基因特异性指南重新分类。从电子病历中收集所有4/5类变异携带者的变异、性别、癌症诊断、诊断年龄和最后已知随访年龄的数据。采用Kaplan-Meier算法计算任何癌症、结直肠癌和子宫内膜癌的累积风险。
共检测到220种不同的PMS2变异。在482名携带者中鉴定出29种4/5类变异。最常见的致病变异是始祖突变c.989-1G＞T，在来自58个家族的204名患者中检测到。482名患者中有87名（18.0%）被诊断为结直肠癌，其中10名（11.8%）在40岁之前被诊断。在我们的队列中，70岁时结直肠癌的累积风险为34.7%，子宫内膜癌为26.1%。
经过15年的基因检测，挪威已检测到29种不同的4/5类变异。几乎一半的挪威PMS2携带者有始祖变异989-1G＞T。我们队列中结直肠癌的外显率中等但存在差异，因为11.5%的确诊患者年龄小于40岁。
