Comprehensive genomic and phenotypic characterization of germline FH deletion in hereditary leiomyomatosis and renal cell carcinoma.
Comprehensive genomic and phenotypic characterization of germline FH deletion in hereditary leiomyomatosis and renal cell carcinoma.
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DOI：
10.1002/gcc.22452
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发表时间：
2017-06
期刊：
影响因子：
--
通讯作者：
Linehan WM
中科院分区：
文献类型：
--
作者：
Vocke CD;Ricketts CJ;Merino MJ;Srinivasan R;Metwalli AR;Middelton LA;Peterson J;Yang Y;Linehan WM
遗传性平滑肌瘤病和肾细胞癌（HLRCC）是一种家族性癌症综合征，与皮肤和子宫平滑肌瘤的发展有关，是2型乳头状肾癌的侵袭性形式。HLRCC的特征是FH基因的种系突变。本研究评估了HLRCC患者FH缺失的患病率和临床表型。对缺乏可检测的生殖系FH基因内突变的具有与HLRCC一致的表型表现的患者进行FH缺失研究。使用比较基因组杂交（CGH）阵列和/或CLIA批准的FH缺失/重复分析的组合对来自13个家族的28例患者进行了评价。在13个UOB家系中发现13个不同的种系缺失，包括11个完全FH基因缺失和2个部分FH基因缺失。8个评估的完全FH缺失的大小从~4.74 Mb到249 kb不等，所有缺失均导致额外的基因丢失。两个部分FH基因缺失被确定，与一个导致的损失外显子1和上游区域的FH基因。28例患者中有9例（32%）被诊断为肾癌，13个家族中有7个（54%）具有完全或部分FH缺失。皮肤和子宫平滑肌瘤的发生率与FH点突变家族相似。HLRCC家族中完全或部分FH基因改变与所有典型HLRCC表现相关，包括2型乳头状肾癌，应在任何有这种疾病风险的患者中进行筛查。
Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a familial cancer syndrome associated with the development of cutaneous and uterine leiomyomas, and an aggressive form of type 2 papillary kidney cancer. HLRCC is characterized by germline mutation of the FH gene. This study evaluated the prevalence and clinical phenotype of FH deletions in HLRCC patients. Patients with phenotypic manifestations consistent with HLRCC who lacked detectable germline FH intragenic mutations were investigated for FH deletion. A series of 28 patients from 13 families were evaluated using a combination of a comparative genomic hybridization (CGH) array and/or CLIA-approved FH deletion/duplication analyses. Thirteen distinct germline deletions were identified in the 13 UOB families, including 11 complete FH gene deletions and 2 partial FH gene deletions. The size of eight evaluated complete FH deletions varied from ~4.74 Mb to 249 kb, with all deletions resulting in additional gene losses. Two partial FH gene deletions were identified, with one resulting in loss of exon 1 and the upstream region of the FH gene only. Kidney cancer was diagnosed in 9 (32%) of 28 patients and 7 (54%) of 13 families possessing either complete or partial FH deletions. Cutaneous and uterine leiomyomas were observed at similar rates to those in FH point mutation families. Complete or partial FH gene alterations in HLRCC families are associated with all of the canonical HLRCC manifestations, including type 2 papillary kidney cancer and should be screened for in any patient at-risk for this disorder.
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DOI：
10.2147/ijnrd.s42097
发表时间：
2014
影响因子：
2
作者：
Schmidt LS;Linehan WM
通讯作者：
Linehan WM
影响因子：
5.6
作者：
Merino, Maria J.;Torres-Cabala, Carlos;Linehan, William Marston
通讯作者：
Linehan, William Marston
影响因子：
5.6
作者：
Trpkov, Kiril;Hes, Ondrej;Gill, Anthony J.
通讯作者：
Gill, Anthony J.
影响因子：
3.5
作者：
Alam, NA;Rowan, AJ;Tomlinson, IPM
通讯作者：
Tomlinson, IPM
影响因子：
50.3
作者：
Ooi, Aikseng;Wong, Jing-Chii;Furge, Kyle A.
通讯作者：
Furge, Kyle A.