Boulouard Flavie, Kasper Edwige, Buisine Marie-Pierre, Lienard Gwendoline, Vasseur Stéphanie, Manase Sandrine, Bahuau Michel, Barouk Simonet Emmanuelle, Bubien Virginie, Coulet Florence, Cusin Véronica, Dhooge Marion, Golmard Lisa, Goussot Vincent, Hamzaoui Nadim, Lacaze Elodie, Lejeune Sophie, Mauillon Jacques, Beaumont Marie-Pascale, Pinson Stéphane, Tlemsani Camille, Toulas Christine, Rey Jean-Marc, Uhrhammer Nancy, Bougeard Gaëlle, Frebourg Thierry, Houdayer Claude, Baert-Desurmont Stéphanie
Department of Genetics, Normandy Center for Genomic and Personalized Medicine, Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Rouen, France.
Comprehensive Cancer Center François Baclesse, Laboratory of Cancer Biology and Genetics, Caen, France.
Clin Genet. 2021 May;99(5):662-672. doi: 10.1111/cge.13925. Epub 2021 Feb 12.
Biallelic pathogenic variants in the NTHL1 (Nth like DNA glycosylase 1) gene cause a recently identified autosomal recessive hereditary cancer syndrome predisposing to adenomatous polyposis and colorectal cancer. Half of biallelic carriers also display multiple colonic or extra-colonic primary tumors, mainly breast, endometrium, urothelium, and brain tumors. Published data designate NTHL1 as an important contributor to hereditary cancers but also underline the scarcity of available informations. Thanks to the French oncogenetic consortium (Groupe Génétique et Cancer), we collected NTHL1 variants from 7765 patients attending for hereditary colorectal cancer or polyposis (n = 3936) or other hereditary cancers (n = 3829). Here, we describe 10 patients with pathogenic biallelic NTHL1 germline variants, that is, the second largest NTHL1 series. All carriers were from the "colorectal cancer or polyposis" series. All nine biallelic carriers who underwent colonoscopy presented adenomatous polyps. For digestive cancers, average age at diagnosis was 56.2 and we reported colorectal, duodenal, caecal, and pancreatic cancers. Extra-digestive malignancies included sarcoma, basal cell carcinoma, breast cancer, urothelial carcinoma, and melanoma. Although tumor risks remain to be precisely defined, these novel data support NTHL1 inclusion in diagnostic panel testing. Colonic surveillance should be conducted based on MUTYH recommendations while extra-colonic surveillance has to be defined.
NTHL1（Nth样DNA糖基化酶1）基因的双等位基因致病性变异导致一种最近发现的常染色体隐性遗传性癌症综合征，易患腺瘤性息肉病和结直肠癌。双等位基因携带者中有一半还表现出多个结肠或结肠外原发性肿瘤，主要是乳腺癌、子宫内膜癌、尿路上皮癌和脑肿瘤。已发表的数据表明NTHL1是遗传性癌症的一个重要因素，但也强调了可用信息的匮乏。多亏了法国肿瘤遗传学联盟（遗传与癌症小组），我们从7765名因遗传性结直肠癌或息肉病（n = 3936）或其他遗传性癌症（n = 3829）前来就诊的患者中收集了NTHL1变异。在此，我们描述了10例携带致病性双等位基因NTHL1种系变异的患者，这是第二大的NTHL1病例系列。所有携带者都来自“结直肠癌或息肉病”系列。所有接受结肠镜检查的9名双等位基因携带者都出现了腺瘤性息肉。对于消化道癌症，诊断时的平均年龄为56.2岁，我们报告了结直肠癌、十二指肠癌、盲肠癌和胰腺癌。消化道外恶性肿瘤包括肉瘤、基底细胞癌、乳腺癌、尿路上皮癌和黑色素瘤。尽管肿瘤风险仍有待精确界定，但这些新数据支持将NTHL1纳入诊断检测面板。应根据MUTYH建议进行结肠监测，而结肠外监测则有待确定。
