Molecular Comparison of Imatinib-Naïve and Resistant Gastrointestinal Stromal Tumors: Differentially Expressed microRNAs and mRNAs
Abstract
:1. Introduction
2. Results
2.1. Differentially Expressed microRNAs between Imatinib-Naïve and Imatinib-Resistant GIST Samples
2.2. mRNA Expression Profiling and Ingenuity Pathway Analyses Reveal Differentially Expressed Genes and Pathways in Imatinib-Naïve and Imatinib-Resistant GIST Samples
2.3. Integration of Differentially Expressed microRNAs and mRNAs into Networks
3. Discussion
4. Materials and Methods
4.1. Patient Samples
4.2. RNA Isolation and microRNA Profiling
4.3. mRNA Expression Analysis
4.4. Quantitative RT-PCR
4.5. Pathway Analysis
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Gastrointestinal Stromal Tumors Imatinib-Naïve (IM-n) | ||||||
Male | n = 23 | |||||
Female | n = 10 | |||||
Median age (range) | 65 (41–85) | |||||
Sample code | KIT mutation status | Location | Risk of malignancy * | miRNA | mRNA | |
X1KIT11 | p.V560D/KIT11 | Small intestine | intermediate | ✓ | ✓ | |
X4KIT11 | p.W557_V559delinsF/KIT11 | Small intestine | high | ✓ | ✓ | |
X6KIT11 | p.W557R/KIT11 | Small intestine | overtly malignant ** | ✓ | ||
X8KIT11 | p.L576_R588dup/KIT11 | Stomach | intermediate | ✓ | ✓ | |
X9.2.KIT11 | p.W557_V559delinsF/KIT11 | Stomach | high | ✓ | ||
X10KIT11 | p.W557R/KIT11 | Stomach | intermediate | ✓ | ||
X12KIT11 | p.K550_V555del/KIT11 | Stomach | high | ✓ | ||
X14KIT11 | p.581_590insKWEFPRNRLS/KIT11 | Stomach | intermediate | ✓ | ✓ | |
X23KIT11 | p.W557_K558del/KIT11 | Stomach | intermediate | ✓ | ||
X24KIT11 | p.V554D/KIT11 | Stomach | intermediate | ✓ | ✓ | |
X25KIT11 | p.W557_G592dup (c.1669_1774 + 2dup)/KIT11 | Stomach | high | ✓ | ||
X26KIT11 | p.K558_V559delinsN (AAT) homo/KIT11 | Mediastinum | high | ✓ | ||
X34KIT11 | p.W557_V560delinsF/KIT11 | Stomach | high | ✓ | ||
X35KIT11 | p.V560D/KIT11 | Stomach | overtly malignant | ✓ | ✓ | |
X39KIT11 | p.L576P/KIT11 | Duodenum | intermediate | ✓ | ✓ | |
X40KIT9 | p.A502_Y503dup/KIT9 | Colon | overtly malignant | ✓ | ||
X45KIT11 | p.K550_K558delinsG/KIT11 | Small intestine | overtly malignant | ✓ | ||
X47KIT11 | p.V559A/KIT11 | Stomach | low | ✓ | ||
X48KIT11 | p.V560A/KIT11 | Duodenum | intermediate | ✓ | ✓ | |
X53KIT11 | p.Q556_V559delinsH; c.1668_1676del9/KIT11 | Stomach | overtly malignant | ✓ | ✓ | |
X55KIT11 | p.W557_K558del/KIT11 | Stomach | intermediate | ✓ | ||
X64KIT11 | p.V560D/KIT11 | Stomach | high | ✓ | ✓ | |
X78KIT11 | p.W557_K558del; c.1669_1674del/KIT11 | Stomach | overtly malignant | ✓ | ✓ | |
X82KIT11 | p.W557_P573delinsFQ/KIT11 | Stomach | overtly malignant | ✓ | ||
X86KIT9 | p.A502_Y503dup/KIT9 | Small intestine | overtly malignant | ✓ | ||
X89KIT17 | p.N822K/KIT17 | Small intestine | overtly malignant | ✓ | ✓ | |
X95KIT11 | p.T574_R586insK/KIT11 | Stomach | intermediate | ✓ | ||
X100KIT9 | p.A502_Y503dup/KIT9 | Small intestine | overtly malignant | ✓ | ||
X101KIT11 | p.E554_K558del/KIT11 | Stomach | low | ✓ | ||
X102KIT11 | p.W557R/KIT11 | Stomach | high | ✓ | ✓ | |
X108KIT9 | p.A502_Y503dup/KIT9 | Small intestine | overtly malignant | ✓ | ✓ | |
X.KIT11 | p.M552_E554delinsK/KIT11 | Small intestine | overtly malignant | ✓ | ||
X119KIT11 | p.Q556_I563del/KIT11 | Stomach | low | ✓ | ||
Gastrointestinal Stromal Tumors Imatinib-Resistant (IM-r) *** | ||||||
Male | n = 14 | |||||
Female | n = 6 | |||||
Median age (range) | 49.5 (22–67) | |||||
Sample code | KIT mutation status | KIT secondary mutation | Location | Risk of malignancy * | miRNA | mRNA |
X2KIT9 | p.A502_Y503dup/KIT9 | Not detected | Colon | overtly malignant | ✓ | ✓ |
X27KIT11 | p.L576P; c.1727 T > C/27KIT11 | p.D820Y; c.2458G > T | Small intestine | overtly malignant | ✓ | ✓ |
X36KIT11 | p.Q556_E561delinsQ/KIT11 | Not detected | Small intestine | overtly malignant | ✓ | ✓ |
X42KIT9 | p.A502_Y503dup/KIT9 | KIT: p.V654A | Small intestine | overtly malignant | ✓ | ✓ |
X44KIT9 | p.A502_Y503dup/KIT9 | Not detected | Small intestine | overtly malignant | ✓ | ✓ |
X54KIT11 | p.K550_K558delinsQ/KIT11 | KIT: p.D820Y | Small intestine | overtly malignant | ✓ | ✓ |
X58KIT11 | p.I563_Q575del/KIT11 | KIT: p.D820Y | Stomach | overtly malignant | ✓ | ✓ |
X70KIT11 | p.E554_D572del/KIT11 | KIT: p.V654A | Small intestine | overtly malignant | ✓ | ✓ |
X71KIT11 | p.V559D/KIT11 | KIT: p.D820G | Small intestine | overtly malignant | ✓ | ✓ |
X73KIT11 | p.N567_L576delinsI/KIT11 | Not detected | Small intestine | overtly malignant | ✓ | ✓ |
X74KIT9 | p.A502_Y503dup/KIT9 | Not detected | Small intestine | overtly malignant | ✓ | |
X77KIT9 | p.A502_Y503dup/KIT9 | Not detected | Small intestine | overtly malignant | ✓ | ✓ |
X85KIT9 | p.A502_Y503dup/KIT9 | Not detected | Small intestine | overtly malignant | ✓ | ✓ |
X91KIT11 | p.K550_K558del/KIT11 | KIT: p.D820Y | Small intestine | overtly malignant | ✓ | |
X104KIT11 | p.W557_K558del/KIT11 | Not detected | Small intestine | overtly malignant | ✓ | ✓ |
X105KIT9 | p.A502_Y503dup/KIT9 | Not detected | Small intestine | overtly malignant | ✓ | ✓ |
X112KIT11 | c.1654_1671del18 (p.M552_W557del)/KIT11 | Not detected | Small intestine | overtly malignant | ✓ | ✓ |
X116KIT11 | p.557_558del homo/KIT11 | Not detected | Small intestine | overtly malignant | ✓ | |
X117KIT11 | p.K550_V555delinsL; c.1648_1663delinsT/KIT11 | p.D820Y; c.2458 G > T | Small intestine | overtly malignant | ✓ | |
X118KIT11 | p.V559D; c.1676 T > A/KIT11 | KIT p.V654A; c.1961 T > C | Small intestine | overtly malignant | ✓ |
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Amirnasr, A.; Gits, C.M.M.; van Kuijk, P.F.; Smid, M.; Vriends, A.L.M.; Rutkowski, P.; Sciot, R.; Schöffski, P.; Debiec-Rychter, M.; Sleijfer, S.; et al. Molecular Comparison of Imatinib-Naïve and Resistant Gastrointestinal Stromal Tumors: Differentially Expressed microRNAs and mRNAs. Cancers 2019, 11, 882. https://doi.org/10.3390/cancers11060882
Amirnasr A, Gits CMM, van Kuijk PF, Smid M, Vriends ALM, Rutkowski P, Sciot R, Schöffski P, Debiec-Rychter M, Sleijfer S, et al. Molecular Comparison of Imatinib-Naïve and Resistant Gastrointestinal Stromal Tumors: Differentially Expressed microRNAs and mRNAs. Cancers. 2019; 11(6):882. https://doi.org/10.3390/cancers11060882
Chicago/Turabian StyleAmirnasr, Azadeh, Caroline M.M. Gits, Patricia F. van Kuijk, Marcel Smid, Anne L.M. Vriends, Piotr Rutkowski, Raf Sciot, Patrick Schöffski, Maria Debiec-Rychter, Stefan Sleijfer, and et al. 2019. "Molecular Comparison of Imatinib-Naïve and Resistant Gastrointestinal Stromal Tumors: Differentially Expressed microRNAs and mRNAs" Cancers 11, no. 6: 882. https://doi.org/10.3390/cancers11060882