Yurchenko Andrey A, Fresneau Brice, Borghese Bruno, Rajabi Fatemeh, Tata Zora, Genestie Catherine, Sarasin Alain, Nikolaev Sergey I
INSERM U981, Gustave Roussy Cancer Campus, Université Paris Saclay, Villejuif, France.
Department of Children and Adolescents Oncology, Gustave Roussy, Villejuif, France.
Commun Med (Lond). 2023 Aug 11;3(1):109. doi: 10.1038/s43856-023-00341-6.
Xeroderma pigmentosum (XP) is a group of rare hereditary disorders with highly increased risk of skin tumors due to defective DNA repair. Recently we reported 34-fold increased risk of internal tumors in XP patients in comparison with general population. The molecular data and clinical practice on the internal tumors treatment in XP patients is limited and scarcely represented in the medical literature. In this work, we describe young patients with constitutive biallelic deactivation of the XPC gene developing gynecological tumors with somatic DICER1 mutations.
Whole genome sequencing was used to analyze in detail somatic mutational landscape and driver events of these rare tumors.
We describe five early-onset gynecological tumors in four xeroderma pigmentosum group C (XP-C) young patients (11 to 19 years old) including vaginal embryonal rhabdomyosarcomas in monozygotic twin sisters, juvenile granulosa-cell tumor of the ovary and poorly differentiated stage IA Sertoli-Leydig cell tumor in 19-years old patient, and FIGO stage IC1 tumor of ovary in 13-years old patient. XP-C ovarian tumors harbor 4.4 times more single base substitutions than sporadic tissue-matched cancers and demonstrate XP-C specific mutation signature with strong transcriptional bias indicating inability of the cells to repair bulky DNA lesions of unknown etiology. A special mode of treatment was applied to avoid usage of chemotherapy which is toxic for XP patients.
XP-C status should be accounted for prevention and specific treatment of gynecological tumors in young DNA repair-deficient XP patients.
着色性干皮病（XP）是一组罕见的遗传性疾病，由于DNA修复缺陷，皮肤肿瘤风险大幅增加。最近我们报告，与普通人群相比，XP患者发生内部肿瘤的风险增加了34倍。关于XP患者内部肿瘤治疗的分子数据和临床实践有限，医学文献中也很少有相关报道。在这项研究中，我们描述了XPC基因双等位基因组成性失活并伴有体细胞DICER1突变的年轻患者发生妇科肿瘤的情况。
采用全基因组测序详细分析这些罕见肿瘤的体细胞突变图谱和驱动事件。
我们描述了4例着色性干皮病C组（XP-C）年轻患者（11至19岁）发生的5例早发性妇科肿瘤，包括单卵双胞胎姐妹中的阴道胚胎性横纹肌肉瘤、19岁患者的卵巢幼年型颗粒细胞瘤和低分化IA期支持-间质细胞瘤，以及13岁患者的FIGO IC1期卵巢肿瘤。XP-C卵巢肿瘤的单碱基替换比散发性组织匹配癌症多4.4倍，并表现出XP-C特异性突变特征，具有强烈的转录偏向性，表明细胞无法修复病因不明的大块DNA损伤。采用了一种特殊的治疗方式以避免使用对XP患者有毒的化疗。
在预防和特异性治疗年轻的DNA修复缺陷型XP患者的妇科肿瘤时，应考虑XP-C状态。
