Yosuke Yamada1,2, Hanibal Bohnenberger3, Mark Kriegsmann4,5, Katharina Kriegsmann6, Peter Sinn4, Norihiro Goto7, Yuki Nakanishi7, Hiroshi Seno7, Yoshitsugu Chigusa8, Masakazu Fujimoto9, Sachiko Minamiguchi9, Hironori Haga9, Ronald Simon10, Guido Sauter10, Philipp Ströbel3, Alexander Marx11. 1. Institute of Pathology, University Medical Centre Mannheim and Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. yyamada@kuhp.kyoto-u.ac.jp. 2. Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan. yyamada@kuhp.kyoto-u.ac.jp. 3. Institute of Pathology, University Medical Center Göttingen, University of Göttingen, Göttingen, Germany. 4. Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany. 5. German Center for Lung Cancer Research (DZL), Heidelberg, Germany. 6. Department of Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany. 7. Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan. 8. Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan. 9. Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan. 10. Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 11. Institute of Pathology, University Medical Centre Mannheim and Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Abstract
BACKGROUND: Tuft cells are chemosensory epithelial cells playing a role in innate immunity. Recent studies revealed cancers with a tuft cell-like gene expression signature in the thorax. We wondered whether this signature might also occur in extrathoracic cancers. METHODS: We examined mRNA expression of tuft cell markers (POU2F3, GFI1B, TRPM5, SOX9, CHAT, and AVIL) in 19 different types of cancers in multiple extrathoracic organs with The Cancer Genome Atlas (TCGA) (N = 6322). Four different extrathoracic cancers in our local archives (N = 909) were analysed by immunohistochemistry. RESULTS: Twenty-two (0.35%) extrathoracic tumours with co-expression of POU2F3 and other tuft cell markers were identified in various TCGA datasets. Twelve of the 22 "tuft cell-like tumours" shared poor differentiation and a gene expression pattern, including KIT, anti-apoptotic BCL2, and ionocyte-associated genes. In our archival cases, eleven (1.21%) tumours co-expressing POU2F3, KIT, and BCL2 on immunohistochemistry, i.e., were presumable tuft cell-like cancers. In three among five TCGA cohorts, the tuft cell-like cancer subsets expressed SLFN11, a promising biomarker of PARP inhibitor susceptibility. CONCLUSIONS: Tuft cell-like carcinomas form distinct subsets in cancers of many organs. It appears warranted to investigate their shared gene expression signature as a predictive biomarker for novel therapeutic strategies.
BACKGROUND: Tuft cells are chemosensory epithelial cells playing a role in innate immunity. Recent studies revealed cancers with a tuft cell-like gene expression signature in the thorax. We wondered whether this signature might also occur in extrathoracic cancers. METHODS: We examined mRNA expression of tuft cell markers (POU2F3, GFI1B, TRPM5, SOX9, CHAT, and AVIL) in 19 different types of cancers in multiple extrathoracic organs with The Cancer Genome Atlas (TCGA) (N = 6322). Four different extrathoracic cancers in our local archives (N = 909) were analysed by immunohistochemistry. RESULTS: Twenty-two (0.35%) extrathoracic tumours with co-expression of POU2F3 and other tuft cell markers were identified in various TCGA datasets. Twelve of the 22 "tuft cell-like tumours" shared poor differentiation and a gene expression pattern, including KIT, anti-apoptotic BCL2, and ionocyte-associated genes. In our archival cases, eleven (1.21%) tumours co-expressing POU2F3, KIT, and BCL2 on immunohistochemistry, i.e., were presumable tuft cell-like cancers. In three among five TCGA cohorts, the tuft cell-like cancer subsets expressed SLFN11, a promising biomarker of PARP inhibitor susceptibility. CONCLUSIONS: Tuft cell-like carcinomas form distinct subsets in cancers of many organs. It appears warranted to investigate their shared gene expression signature as a predictive biomarker for novel therapeutic strategies.