Identification of Fusion Genes and Targets for Genetically Matched Therapies in a Large Cohort of Salivary Gland Cancer Patients
Abstract
:Simple Summary
Abstract
1. Introduction
2. Methods
2.1. Patient Selection and Material Acquisition
2.2. DNA and RNA Extraction
2.3. Detection of RNA Gene Fusion Transcripts
2.4. DNA Next Generation Sequencing
2.5. Pan-TRK Immunohistochemistry
2.6. NTRK1, NTRK2 and NTRK3 Fluorescence In Situ Hybridization
2.7. TSO500 Data Analysis
2.8. Data Analysis
3. Results
3.1. Included Patients Comprise Diverse Subtypes of Salivary Gland Cancer
3.2. Half of SGC Cases Harbor Gene Fusions with Varying Incidence among Subtypes
3.3. Frequent Detection of MYB- and MYBL1-NFIB Fusion Transcripts in AdCC
3.4. A Plethora of Both Known and New Fusion Transcripts was Detected in Non-AdCC Cases
3.5. Pan-TRK Immunohistochemistry Is False Positive in the Majority of SGC Cases
3.6. High TMB and MSI Are Rare in SGC
3.7. Pathogenic Small Nucleotide Variants Are Most Frequent in SDC
3.8. Copy Number Variants Are Mostly Restricted to ERBB2 Amplifications in SDC
3.9. DNA and RNA Analysis Reveals Actionable Targets in the Majority of SGC Cases
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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All (n = 121) | AdCC (n = 46) | SDC (n = 44) | MEC (n = 16) | AciCC (n = 9) | Misc. (n = 6) | ||
---|---|---|---|---|---|---|---|
n (%) | |||||||
Age at diagnosis | |||||||
Median (range) | 57 (17–90) | 53 (21–83) | 63 (35–90) | 53 (17–72) | 56 (45–71) | 67 (48–79) | |
Gender | |||||||
Male | 58 (47.9) | 15 (32.6) | 28 (63.6) | 8 (50) | 5 (55.6) | 2 (33.3) | |
Female | 63 (52.1) | 31 (67.4) | 16 (36.4) | 8 (50) | 4 (44.4) | 4 (66.7) | |
Location primary tumor | |||||||
Major salivary gland | 81 (66.9) | 21 (45.7) | 42 (95.5) | 6 (37.5) | 9 (100.0) | 3 (50.0) | |
Minor salivary gland | 28 (23.1) | 16 (34.8) | 1 (2.3) | 8 (50.0) | 0 (0.0) | 3 (50.0) | |
Other | 12 (9.9) | 9 (19.6) | 1 (2.3) | 2 (12.5) | 0 (0.0) | 0 (0.0) | |
T-stage at diagnosis | |||||||
1–2 | 39 (32.3) | 6 (13.0) | 16 (36.4) | 10 (62.5) | 4 (44.4) | 3 (50.0) | |
3–4 | 56 (46.3) | 27 (58.7) | 21 (47.7) | 4 (25.0) | 2 (22.2) | 2 (33.3) | |
Tx | 26 (21.5) | 13 (28.3) | 7 (15.9) | 2 (12.5) | 3 (33.3) | 1 (16.7) | |
N-stage at diagnosis | |||||||
0 | 52 (43.0) | 27 (58.7) | 8 (18.2) | 7 (43.8) | 5 (55.6) | 5 (83.3) | |
1–3 | 44 (36.4) | 7 (15.2) | 28 (63.6) | 7 (43.8) | 1 (11.1) | 1 (16.7) | |
Nx | 25 (20.7) | 12 (26.1) | 8 (18.2) | 2 (12.5) | 3 (33.3) | 0 (0.0) | |
M-stage at diagnosis | |||||||
0 | 100 (82.6) | 36 (78.3) | 39 (88.6) | 14 (87.5) | 7 (77.8) | 4 (66.7) | |
1 | 19 (15.7) | 8 (17.4) | 5 (11.4) | 2 (12.5) | 2 (22.2) | 2 (33.3) | |
Mx | 2 (1.7) | 2 (4.3) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | |
Initial treatment intent | |||||||
Curative | 99 (83.5) | 35 (76.1) | 39 (88.6) | 14 (87.5) | 7 (77.8) | 4 (66.7) | |
Palliative | 22 (18.2) | 11 (23.9) | 5 (11.4) | 2 (12.5) | 2 (22.2) | 2 (33.3) | |
R/M disease after initial curative treatment (n = 99) | |||||||
Yes | 63 (63.4) | 28 (80.0) | 24 (61.5) | 6 (42.9) | 4 (57.1) | 1 (25%) | |
No | 36 (36.4) | 7 (20.0) | 15 (38.5) | 8 (57.1) | 3 (42.9) | 3 (75%) | |
Underwent surgery primary tumor | |||||||
Yes | 101 (83.5) | 36 (78.3) | 38 (86.4) | 15 (93.8) | 8 (88.9) | 4 (66.7) | |
No | 20 (16.5) | 10 (21.7) | 6 (13.6) | 1 (6.3) | 1 (11.1) | 2 (33.3) | |
Palliative systemic therapy | |||||||
Yes | 57 (47.1) | 18 (39.1) | 28 (63.6) | 4 (25.0) | 5 (55.6) | 2 (33.3) | |
No | 64 (52.9) | 28 (60.9) | 16 (36.4) | 12 (75.0) | 4 (44.4) | 4 (66.7) | |
Lines of systemic therapy | |||||||
Median (range) | 1 (1–7) | 1 (1–4) | 2 (1–5) | 2 (1–7) | 2 (1–2) | 1 (1) | |
First line systemic therapy | |||||||
Chemotherapy | 18 (14.9) | 11 (23.9) | 2 (4.5) | 2 (12.5) | 3 (33.3) | 0 (0.0) | |
Targeted | 12 (9.9) | 6 (13.0) | 1 (2.3) | 2 (12.5) | 1 (11.1) | 2 (33.3) | |
Hormonal | 17 (14.0) | 0 (0.0) | 16 (36.4) | 0 (0.0) | 1 (11.1) | 0 (0.0) | |
Immunotherapy | 1 (0.8) | 0 (0.0) | 1 (2.3) | 0 (0.0) | 0 (0.0) | 0 (0.0) | |
Combination | 8 (6.6) | 0 (0.0) | 8 (18.2) | 0 (0.0) | 0 (0.0) | 0 (0.0) | |
Other | 1 (0.8) | 1 (2.2) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
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Lassche, G.; van Helvert, S.; Eijkelenboom, A.; Tjan, M.J.H.; Jansen, E.A.M.; van Cleef, P.H.J.; Verhaegh, G.W.; Kamping, E.J.; Grünberg, K.; van Engen-van Grunsven, A.C.H.; et al. Identification of Fusion Genes and Targets for Genetically Matched Therapies in a Large Cohort of Salivary Gland Cancer Patients. Cancers 2022, 14, 4156. https://doi.org/10.3390/cancers14174156
Lassche G, van Helvert S, Eijkelenboom A, Tjan MJH, Jansen EAM, van Cleef PHJ, Verhaegh GW, Kamping EJ, Grünberg K, van Engen-van Grunsven ACH, et al. Identification of Fusion Genes and Targets for Genetically Matched Therapies in a Large Cohort of Salivary Gland Cancer Patients. Cancers. 2022; 14(17):4156. https://doi.org/10.3390/cancers14174156
Chicago/Turabian StyleLassche, Gerben, Sjoerd van Helvert, Astrid Eijkelenboom, Martijn J. H. Tjan, Erik A. M. Jansen, Patricia H. J. van Cleef, Gerald W. Verhaegh, Eveline J. Kamping, Katrien Grünberg, Adriana C. H. van Engen-van Grunsven, and et al. 2022. "Identification of Fusion Genes and Targets for Genetically Matched Therapies in a Large Cohort of Salivary Gland Cancer Patients" Cancers 14, no. 17: 4156. https://doi.org/10.3390/cancers14174156
APA StyleLassche, G., van Helvert, S., Eijkelenboom, A., Tjan, M. J. H., Jansen, E. A. M., van Cleef, P. H. J., Verhaegh, G. W., Kamping, E. J., Grünberg, K., van Engen-van Grunsven, A. C. H., Ligtenberg, M. J. L., & van Herpen, C. M. L. (2022). Identification of Fusion Genes and Targets for Genetically Matched Therapies in a Large Cohort of Salivary Gland Cancer Patients. Cancers, 14(17), 4156. https://doi.org/10.3390/cancers14174156