Genomic architecture of FGFR2 fusions in cholangiocarcinoma and its implication for molecular testing

被引：43

作者：

Neumann, Olaf ^{[1
,2
,3
]}

Burn, Timothy C. ^{[4
,14
]}

Allgaeuer, Michael ^{[1
]}

Ball, Markus ^{[1
,5
]}

Kirchner, Martina ^{[1
]}

Albrecht, Thomas ^{[1
]}

Volckmar, Anna-Lena ^{[1
]}

Beck, Susanne ^{[1
]}

Endris, Volker ^{[1
]}

Goldschmid, Hannah ^{[1
]}

Lehmann, Ulrich ^{[6
]}

Seker-Cin, Huriye ^{[1
]}

Uhrig, Sebastian ^{[7
,8
]}

Roessler, Stephanie ^{[1
]}

Budczies, Jan ^{[1
,2
]}

Froehling, Stefan ^{[2
,3
,8
,9
]}

Longerich, Thomas ^{[1
,10
]}

Wagner, Alex H. ^{[11
,12
]}

Vogel, Arndt ^{[13
]}

Schirmacher, Peter ^{[1
,2
,3
,10
]}

Stenzinger, Albrecht ^{[1
,2
,3
,5
]}

Kazdal, Daniel ^{[1
,2
,3
,5
]}

机构：

[1] Univ Hosp Heidelberg, Inst Pathol, Heidelberg, Germany

[2] Ctr Personalized Med Heidelberg ZPM, Heidelberg, Germany

[3] German Canc Consortium DKTK, Heidelberg, Germany

[4] Incyte Res Inst, Wilmington, DE USA

[5] German Ctr Lung Res DZL, Translat Lung Res Ctr TLRC Heidelberg, Heidelberg, Germany

[6] Hannover Med Sch, Inst Pathol, Hannover, Germany

[7] Natl Ctr Tumor Dis NCT Heidelberg, Mol Precis Oncol Program, Computat Oncol Grp, Heidelberg, Germany

[8] German Canc Res Ctr, Heidelberg, Germany

[9] Natl Ctr Tumor Dis NCT Heidelberg, Dept Translat Med Oncol, Heidelberg, Germany

[10] Liver Canc Ctr Heidelberg, Heidelberg, Germany

[11] Nationwide Childrens Hosp, Steve & Cindy Rasmussen Inst Genom Med, Columbus, OH USA

[12] Ohio State Univ, Coll Med, Dept Pediat & Biomed Informat, Columbus, OH 43210 USA

[13] Hannover Med Sch, Gastroenterol Hepatol & Endocrinol, Hannover, Germany

[14] Tyra Biosci, Carlsbad, CA USA

来源：

BRITISH JOURNAL OF CANCER | 2022年 / 127卷 / 08期

关键词：

GROWTH-FACTOR RECEPTORS; METASTATIC CHOLANGIOCARCINOMA; GENE FUSIONS; OPEN-LABEL; TRANSLOCATIONS; MULTICENTER; MUTATIONS; RNA;

D O I：

10.1038/s41416-022-01908-1

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background Cholangiocarcinoma (CCA) is a primary malignancy of the biliary tract with a dismal prognosis. Recently, several actionable genetic aberrations were identified with significant enrichment in intrahepatic CCA, including FGFR2 gene fusions with a prevalence of 10-15%. Recent clinical data demonstrate that these fusions are druggable in a second-line setting in advanced/metastatic disease and the efficacy in earlier lines of therapy is being evaluated in ongoing clinical trials. This scenario warrants standardised molecular profiling of these tumours. Methods A detailed analysis of the original genetic data from the FIGHT-202 trial, on which the approval of Pemigatinib was based, was conducted. Results Comparing different detection approaches and displaying representative cases, we described the genetic landscape and architecture of FGFR2 fusions in iCCA and show biological and technical aspects to be considered for their detection. We elaborated parameters, including a suggestion for annotation, that should be stated in a molecular diagnostic FGFR2 report to allow a complete understanding of the analysis performed and the information provided. Conclusion This study provides a detailed presentation and dissection of the technical and biological aspects regarding FGFR2 fusion detection, which aims to support molecular pathologists, pathologists and clinicians in diagnostics, reporting of the results and decision-making.

引用

页码：1540 / 1549

页数：10

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