Clinicopathological and molecular characteristics of RSPO fusion-positive colorectal cancer
Clinicopathological and molecular characteristics of RSPO fusion-positive colorectal cancer
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RSPO融合阳性结直肠癌的临床病理和分子特征
DOI：
10.1038/s41416-022-01880-w
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Shiraishi K. and Sekine S.
中科院分区：
文献类型：
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作者：
Hashimoto T.;Takayanagi D.;Yonemaru J.;Naka T.;Nagashima K.;Yatabe Y.;Shida D.;Hamamoto R.;Kleeman S. O.;Leedham S. J.;Maughan T.;Takashima A.;Shiraishi K. and Sekine S.
背景导致WNT通路激活的RSPO融合是结直肠癌(CRC)潜在的治疗靶点，但其临床病理意义尚不清楚。对RSPO融合阳性的肿瘤进行全外显子组测序。结果我们的分析鉴定出29例RSPO融合(2.8%)，其中5例EIF3E-RSPO2融合，24例PTPRK-RSPO2融合。患者包括17名女性和12名男性。13个肿瘤(45%)位于右侧。组织学上，大约一半的肿瘤(13/29，45%)有灶性或广泛的粘液成分，明显高于RSPO融合阴性的肿瘤(13%；P= 8.1 × 10−7)。4个肿瘤(14%)是错配修复缺陷。WES在总共27个肿瘤中发现了KRAS、BRAF和NRAS突变(93%)。相比之下，主要的WNT途径基因如APC、CTNNB1和RNF43的致病突变缺失。RSPO融合状态对总体或无复发生存率没有统计学意义的影响。这些临床病理和遗传学特征在以往研究的综合分析中也得到了证实。结论RSPO融合阳性的大肠癌是一种罕见的大肠癌亚群，具有几个典型的临床病理和遗传学特征。
BackgroundRSPOfusions that lead to WNT pathway activation are potential therapeutic targets in colorectal cancer (CRC), but their clinicopathological significance remains unclear.MethodsWe screened 1019 CRCs forRSPOfusions using multiplex reverse transcription–PCR. TheRSPOfusion-positive tumours were subjected to whole-exome sequencing (WES).ResultsOur analysis identified 29 CRCs withRSPOfusions (2.8%), consisting of five with anEIF3E-RSPO2fusion and 24 withPTPRK-RSPO3fusions. The patients were 17 women and 12 men. Thirteen tumours (45%) were right-sided. Histologically, approximately half of the tumours (13/29, 45%) had a focal or extensive mucinous component that was significantly more frequent than theRSPOfusion-negative tumours (13%;P= 8.1 × 10−7). Four tumours (14%) were mismatch repair-deficient. WES identifiedKRAS,BRAF, andNRASmutations in a total of 27 tumours (93%). In contrast, pathogenic mutations in major WNT pathway genes, such asAPC,CTNNB1andRNF43, were absent.RSPOfusion status did not have a statistically significant influence on the overall or recurrence-free survival. These clinicopathological and genetic features were also confirmed in a pooled analysis of previous studies.ConclusionRSPOfusion-positive CRCs constitute a rare subgroup of CRCs with several characteristic clinicopathological and genetic features.
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影响因子：
4.6
作者：
Fischer MM;Yeung VP;Cattaruzza F;Hussein R;Yen WC;Murriel C;Evans JW;O'Young G;Brunner AL;Wang M;Cain J;Cancilla B;Kapoun A;Hoey T
通讯作者：
Hoey T
影响因子：
3.5
作者：
Mizuguchi, Yasuhiko;Sakamoto, Taku;Sekine, Shigeki
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Sekine, Shigeki
日本人群中 NTRK 融合阳性结直肠癌
影响因子：
2.2
作者：
Yonemaru Junpei;Hashimoto Taiki;Takayanagi Daisuke;Naka Tomoaki;Yatabe Yasushi;Kanemitsu Yukihide;Shiraishi Kouya;Sekine Shigeki
通讯作者：
Sekine Shigeki
影响因子：
5.2
作者：
Kleeman SO;Leedham SJ
通讯作者：
Leedham SJ
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