Vocke Cathy D, Ricketts Christopher J, Ball Mark W, Schmidt Laura S, Metwalli Adam R, Middelton Lindsay A, Killian J Keith, Khan Javed, Meltzer Paul S, Simonds William F, Merino Maria J, Linehan W Marston
Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD; Basic Science Program and Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD.
Urology. 2019 Feb;124:91-97. doi: 10.1016/j.urology.2018.11.013. Epub 2018 Nov 16.
To describe a family in which 3 members presented with mixed epithelial tumor of the kidney (MEST) and were found to possess a germline mutation in CDC73, a gene which is associated with hyperparathyroidism-jaw tumor syndrome (HPT-JT).
Blood and tumor DNA from three family members who presented with a primary diagnosis of MEST was subjected to targeted gene sequencing to identify potential genetic components.
A germline start codon mutation (p.M1I) in CDC73 was identified in all 3 family members who presented with MEST and 2 tumors from 1 patient demonstrated somatic copy-neutral loss of heterozygosity. Patients presented with no evidence of hyperparathyroidism or jaw tumors, but both female patients had hysterectomies at an early age due to excessive bleeding and numerous fibroids, which is common in HPT-JT. A germline p.M1I mutation has been previously reported in a family with clinical features of HPT-JT.
Patients with MEST may be at risk for HPT-JT and CDC73 germline mutation testing of MEST patients should be considered.
描述一个有3名成员患肾混合上皮瘤（MEST）的家族，并发现他们携带与甲状旁腺功能亢进-颌骨肿瘤综合征（HPT-JT）相关的基因CDC73的种系突变。
对3名初步诊断为MEST的家族成员的血液和肿瘤DNA进行靶向基因测序，以确定潜在的遗传成分。
在所有3名患MEST的家族成员中均鉴定出CDC73的种系起始密码子突变（p.M1I），1例患者的2个肿瘤显示体细胞拷贝中性杂合性缺失。患者无甲状旁腺功能亢进或颌骨肿瘤的证据，但两名女性患者因出血过多和多发性肌瘤在早年进行了子宫切除术，这在HPT-JT中很常见。先前在一个具有HPT-JT临床特征的家族中报道过种系p.M1I突变。
MEST患者可能有患HPT-JT的风险，应考虑对MEST患者进行CDC73种系突变检测。
