NCOA4-RET and TRIM27-RET Are Characteristic Gene Fusions in Salivary Intraductal Carcinoma, Including Invasive and Metastatic Tumors

Abstract:
Abstract: Intraductal carcinoma (IC) is the new WHO designation for tumors previously encompassed by “low-grade cribriform cystadenocarcinoma” and “low-grade salivary duct carcinoma.” The relationship of IC to salivary duct carcinoma (SDC) is controversial, even though they are considered to be distinct entities. IC is a rare low-grade malignant salivary gland neoplasm with histopathological features reminiscent of atypical ductal hyperplasia or ductal carcinoma in situ of the breast, showing diffuse S100 protein and mammaglobin positivity, while it is partially defined genetically. Recently, RET rearrangements including NCOA4-RET and TRIM27-RET have been described in IC. Here, we genetically characterize the largest cohort of IC to date (33 cases) including 8 cases with focal or widespread invasive growth and 1 case with lymph node metastasis. Thirty-three cases of IC were analyzed by next-generation sequencing (NGS) using the FusionPlex Solid Tumor kit (ArcherDX). Identified gene fusions were confirmed using fluorescence in situ hybridization break-apart and fusion probes and an reverse transcription polymerase chain reaction designed specifically for the detected breakpoints. Ten cases of SDC were analyzed for comparison using NGS panels that detect mutations and fusion transcripts. NGS analysis detected an NCOA4-RET fusion transcript in 11 cases of intercalated duct-type IC joining exon 7 or 8 of NCOA4 gene and exon 12 of the RET gene. Eight cases of IC had an invasive growth pattern, including one with widespread invasion and lymph node metastasis. Three invasive ICs harbored an NCOA4-RET fusion transcript, while 1 case was negative, and 2 cases were not analyzable. In addition, a novel TRIM27-RET fusion transcript between exon 3 of TRIM27 and exon 12 of RET was identified in 2 cases of IC with apocrine features, and one of them displayed invasive growth. Two IC cases with invasive growth harbored novel fusions TUT1-ETV5 and KIAA1217-RET, respectively. A total of 42.4% of the cases in this series of IC harbored fusions involving RET. Such fusion transcripts were not detected in any of the 10 SDC cases. We have confirmed NCOA4-RET as a predominant fusion in intercalated duct-type IC, including 3 cases with invasive growth pattern. A novel finding in our series was a case of widely invasive intercalated duct-type IC, with a single lymph node metastasis that revealed an NCOA4-RET fusion transcript. We also demonstrated that a subset of apocrine ICs harbored a TRIM27-RET gene fusion, including one case with invasive growth. In contrast, neither NCOA4-RET nor TRIM27-RET fusions were detected in any tested SDCs. Thus, the distinct molecular findings in IC and SDC support that the tumors are separate malignant salivary tumor entities. The presence of tumor-type–specific NCOA4-RET or TRIM27-RET translocations in a subset of widely invasive carcinomas with intercalated duct-like immunoprofiles suggests that a recharacterization of IC including its redesignation as “intercalated duct carcinoma, invasive or noninvasive” may be appropriate.
Author Listing: Alena Skálová;Nikola Ptáková;Thalita Santana;Abbas Agaimy;Stephan Ihrler;Emmanuelle Uro-Coste;Lester D R Thompson;Justin A Bishop;Martina Baněčkova;Niels J Rupp;Patrizia Morbini;Stefano de Sanctis;Marco Schiavo-Lena;Tomas Vanecek;Michal Michal;Ilmo Leivo
Volume: 43
Pages: 1303 - 1313
DOI: 10.1097/PAS.0000000000001301
Language: English
Journal: The American Journal of Surgical Pathology

AMERICAN JOURNAL OF SURGICAL PATHOLOGY

AM J SURG PATHOL

影响因子:4.5 是否综述期刊:是 是否OA:否 是否预警:不在预警名单内 发行时间:1977 ISSN:0147-5185 发刊频率:Monthly 收录数据库:SCIE/Scopus收录 出版国家/地区:UNITED STATES 出版社:Lippincott Williams and Wilkins Ltd.

期刊介绍

The American Journal of Surgical Pathology has achieved worldwide recognition for its outstanding coverage of the state of the art in human surgical pathology. In each monthly issue, experts present original articles, review articles, detailed case reports, and special features, enhanced by superb illustrations. Coverage encompasses technical methods, diagnostic aids, and frozen-section diagnosis, in addition to detailed pathologic studies of a wide range of disease entities.Official Journal of The Arthur Purdy Stout Society of Surgical Pathologists and The Gastrointestinal Pathology Society.

《美国外科病理学杂志》因其对人类外科病理学最新技术水平的杰出报道而获得了世界范围的认可。在每一期月刊中,专家们都会发表原创文章、评论文章、详细的病例报告和特别报道,并配以精美的插图。除了广泛疾病实体的详细病理学研究外,覆盖范围还包括技术方法、诊断辅助和冷冻切片诊断。亚瑟·珀迪·斯托特外科病理学家学会和胃肠病理学会的官方杂志。

年发文量 147
国人发稿量 11
国人发文占比 7.48%
自引率 6.7%
平均录取率 约5%
平均审稿周期 平均1月
版面费 -
偏重研究方向 医学-病理学
期刊官网 http://journals.lww.com/ajsp/Pages/default.aspx
投稿链接 https://www.editorialmanager.com/AJSP

质量指标占比

研究类文章占比 OA被引用占比 撤稿占比 出版后修正文章占比
98.64% 6.01% 0.00% 0.00%

相关指数

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期刊预警不是论文评价,更不是否定预警期刊发表的每项成果。《国际期刊预警名单(试行)》旨在提醒科研人员审慎选择成果发表平台、提示出版机构强化期刊质量管理。

预警期刊的识别采用定性与定量相结合的方法。通过专家咨询确立分析维度及评价指标,而后基于指标客观数据产生具体名单。

具体而言,就是通过综合评判期刊载文量、作者国际化程度、拒稿率、论文处理费(APC)、期刊超越指数、自引率、撤稿信息等,找出那些具备风险特征、具有潜在质量问题的学术期刊。最后,依据各刊数据差异,将预警级别分为高、中、低三档,风险指数依次减弱。

《国际期刊预警名单(试行)》确定原则是客观、审慎、开放。期刊分区表团队期待与科研界、学术出版机构一起,夯实科学精神,打造气正风清的学术诚信环境!真诚欢迎各界就预警名单的分析维度、使用方案、值得关切的期刊等提出建议!

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2024年02月发布的2024版 不在预警名单中
2023年01月发布的2023版 不在预警名单中
2021年12月发布的2021版 不在预警名单中
2020年12月发布的2020版 不在预警名单中

JCR分区 WOS分区等级:Q1区

版本 按学科 分区
WOS期刊SCI分区
WOS期刊SCI分区是指SCI官方(Web of Science)为每个学科内的期刊按照IF数值排 序,将期刊按照四等分的方法划分的Q1-Q4等级,Q1代表质量最高,即常说的1区期刊。
(2021-2022年最新版)
SURGERY Q1
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关于2019年中科院分区升级版(试行)

分区表升级版(试行)旨在解决期刊学科体系划分与学科发展以及融合趋势的不相容问题。由于学科交叉在当代科研活动的趋势愈发显著,学科体系构建容易引发争议。为了打破学科体系给期刊评价带来的桎梏,“升级版方案”首先构建了论文层级的主题体系,然后分别计算每篇论文在所属主题的影响力,最后汇总各期刊每篇论文分值,得到“期刊超越指数”,作为分区依据。

分区表升级版(试行)的优势:一是论文层级的主题体系既能体现学科交叉特点,又可以精准揭示期刊载文的多学科性;二是采用“期刊超越指数”替代影响因子指标,解决了影响因子数学性质缺陷对评价结果的干扰。整体而言,分区表升级版(试行)突破了期刊评价中学科体系构建、评价指标选择等瓶颈问题,能够更为全面地揭示学术期刊的影响力,为科研评价“去四唯”提供解决思路。相关研究成果经过国际同行的认可,已经发表在科学计量学领域国际重要期刊。

《2019年中国科学院文献情报中心期刊分区表升级版(试行)》首次将社会科学引文数据库(SSCI)期刊纳入到分区评估中。升级版分区表(试行)设置了包括自然科学和社会科学在内的18个大类学科。基础版和升级版(试行)将过渡共存三年时间,推测在此期间各大高校和科研院所仍可能会以基础版为考核参考标准。 提示:中科院分区官方微信公众号“fenqubiao”仅提供基础版数据查询,暂无升级版数据,请注意区分。

中科院分区 查看说明

版本 大类学科 小类学科 Top期刊 综述期刊
医学
1区
SURGERY
外科
1区
PATHOLOGY
病理学
1区
2021年12月
基础版
医学
2区
SURGERY
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1区
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病理学
2区
2021年12月
升级版
医学
1区
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外科
1区
PATHOLOGY
病理学
1区
2020年12月
旧的升级版
医学
1区
SURGERY
外科
1区
PATHOLOGY
病理学
1区
2022年12月
最新升级版
医学
1区
SURGERY
外科
1区
PATHOLOGY
病理学
1区