TCEB1-mutated renal cell carcinoma: a distinct genomic and morphological subtype.
TCEB1-mutated renal cell carcinoma: a distinct genomic and morphological subtype.
复制标题
DOI：
10.1038/modpathol.2015.6
复制
发表时间：
2015-06
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
综合测序分析确定了一组透明细胞肾细胞癌中的肿瘤，其特征在于TCEB 1（一种有助于VHL复合物泛素化缺氧诱导因子的基因）的热点突变。我们分析了来自两个不同队列的11例TCEB 1突变沿着扩展队列的肿瘤，以评估这些肿瘤是否应被视为与透明细胞肾细胞癌和透明细胞乳头状肾细胞癌不同的实体。所有肿瘤的特征在于TCEB 1 Y 79 C/S/F/N或A100 P中的热点突变。肿瘤的形态学和免疫组化特征由两位经验丰富的泌尿生殖系病理学家进行评估。将临床和病理变量、拷贝数改变、突变和表达特征与TCEB 1野生型肿瘤组进行比较。所有TCEB 1突变的肿瘤均为VHL和PBRM 1野生型，并含有不同的拷贝数谱，包括8号染色体杂合性丢失，TCEB 1的位置（8q21.11）。所有肿瘤均缺乏透明细胞肾细胞癌特征3 p缺失，并含有不同的基因表达特征。透明细胞乳头状肿瘤均不携带TCEB 1突变。在病理学上，TCEB 1突变的肿瘤都具有共同的特征，包括横切肿瘤的厚纤维肌带，纯透明细胞细胞学检查，细胞经常显示大量的细胞质，透明细胞肾细胞癌样腺泡区域与折叠管状和局灶性乳头状结构相关。大量细胞质的存在，肿瘤细胞核的管腔极化的情况下，缺乏广泛的杯状分布的碳酸酐酶IX表达区分它与透明细胞乳头状癌。末次随访（中位48个月）时，无患者发生转移。总之，TCEB 1突变的肾细胞癌是一个独特的实体与复发热点突变，特定的拷贝数改变，途径激活和特征性形态学特征。需要进一步的临床随访来确定这些肿瘤是否比传统的透明细胞肾细胞癌更惰性。
Integrated sequencing analysis identified a group of tumors among clear cell renal cell carcinomas characterized by hotspot mutations in TCEB1 (a gene that contributes to the VHL complex to ubiquitinate hypoxia inducible factor). We analyzed 11 tumors from two distinct cohorts with TCEB1 mutations along with an expanded cohort to assess whether these should be considered an entity distinct from clear cell renal cell carcinoma and clear cell papillary renal cell carcinoma. All tumors were characterized by hotspot mutations in TCEB1 Y79C/S/F/N or A100P. Morphologic and immunohistochemical characteristics of the tumors were assessed by two experienced genitourinary pathologists. Clinical and pathologic variables, copy number alterations, mutations and expression signatures were compared to a cohort of TCEB1 wild type tumors. All TCEB1 mutated tumors were VHL and PBRM1 wild type and contained distinct copy number profiles including loss of heterozygosity of chromosome 8, the location of TCEB1 (8q21.11). All tumors lacked the clear cell renal cell carcinoma signature 3p loss and contained distinct gene expression signatures. None of the clear cell papillary tumor harbored TCEB1 mutations. Pathologically, TCEB1-mutated tumors all shared characteristic features including thick fibromuscular bands transecting the tumor, pure clear cell cytology frequently with cells showing voluminous cytoplasm, clear cell renal cell carcinoma-like acinar areas associated with in-folding tubular and focally papillary architecture. The presence of voluminous cytoplasm, absence of luminal polarization of tumor nuclei and lack of extensive cup-like distribution of carbonic anhydrase IX expression distinguish it from clear cell papillary carcinoma. No patients had developed metastases at last follow-up (median 48 months). In sum, TCEB1-mutated renal cell carcinoma is a distinct entity with recurrent hotspot mutations, specific copy number alterations, pathway activation and characteristic morphologic features. Further clinical followup is needed to determine whether these tumors are more indolent compared to conventional clear cell renal cell carcinoma.
登录
查看更多内容
DOI：
10.1158/1078-0432.ccr-12-3886
发表时间：
2013-06-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Hakimi AA;Ostrovnaya I;Reva B;Schultz N;Chen YB;Gonen M;Liu H;Takeda S;Voss MH;Tickoo SK;Reuter VE;Russo P;Cheng EH;Sander C;Motzer RJ;Hsieh JJ;ccRCC Cancer Genome Atlas (KIRC TCGA) Research Network investigators
通讯作者：
ccRCC Cancer Genome Atlas (KIRC TCGA) Research Network investigators
影响因子：
64.8
作者：
Varela, Ignacio;Tarpey, Patrick;Raine, Keiran;Huang, Dachuan;Ong, Choon Kiat;Stephens, Philip;Davies, Helen;Jones, David;Lin, Meng-Lay;Teague, Jon;Bignell, Graham;Butler, Adam;Cho, Juok;Dalgliesh, Gillian L.;Galappaththige, Danushka;Greenman, Chris;Hardy, Claire;Jia, Mingming;Latimer, Calli;Lau, King Wai;Marshall, John;McLaren, Stuart;Menzies, Andrew;Mudie, Laura;Stebbings, Lucy;Largaespada, David A.;Wessels, L. F. A.;Richard, Stephane;Kahnoski, Richard J.;Anema, John;Tuveson, David A.;Perez-Mancera, Pedro A.;Mustonen, Ville;Fischer, Andrej;Adams, David J.;Rust, Alistair;Chan-on, Waraporn;Subimerb, Chutima;Dykema, Karl;Furge, Kyle;Campbell, Peter J.;Teh, Bin Tean;Stratton, Michael R.;Futreal, P. Andrew
通讯作者：
Futreal, P. Andrew
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
11.2
作者：
Beroukhim R;Brunet JP;Di Napoli A;Mertz KD;Seeley A;Pires MM;Linhart D;Worrell RA;Moch H;Rubin MA;Sellers WR;Meyerson M;Linehan WM;Kaelin WG Jr;Signoretti S
通讯作者：
Signoretti S
DOI：
10.1016/s1470-2045(12)70584-3
发表时间：
2013-02
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Kapur P;Peña-Llopis S;Christie A;Zhrebker L;Pavía-Jiménez A;Rathmell WK;Xie XJ;Brugarolas J
通讯作者：
Brugarolas J