Distinct Mutational Profile of Lynch Syndrome Colorectal Cancers Diagnosed under Regular Colonoscopy Surveillance
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients and Tumor Samples
2.2. Histopathology Analysis
2.3. Mutation Analysis
2.4. Immunohistochemical Staining and Quantification of T Cell Density
2.5. Statistical Calculations
3. Results
3.1. Clinical Characteristics
3.2. Histopathology of Incident Cancers
3.3. Mutational Profile and MMR Deficiency Signatures in Incident Cancers
3.4. CMS Analysis in Incident Cancers
3.5. Immune Infiltration and Immune Evasion in Incident Cancers
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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Patient | Age at Diagnosis | Gender | Location | TNM Stage | UICC Stage | Gene | Age at Last FU | Age at Death | Cause of Death | Months Since Last Colonoscopy | Reason of Examination | Finding at Last Colonoscopy * |
---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | 54.6 | M | splenic flexure | T2N0M0 | I | MLH1 | 62.9 | 21.0 | symptoms | 0 | ||
2 | 61.7 | F | ascendens | T1N0M0 | I | MLH1 | 76.5 | 20.3 | follow-up | advanced adenoma | ||
3 | 44.2 | M | descendens | Dukes A | I | MLH1 | 55.1 | 36.0 | follow-up | adenoma with LG dysplasia | ||
4 | 69.7 | F | sigmoid | T1N0M0 | I | MSH2 | 74.9 | 75.1 | cardiac insufficiency | 7.3 | follow-up | advanced adenoma |
5 | 63.1 | F | tranverse | T3N0M0 | II | MSH2 | 72.6 | 72.6 | pancreatic cancer | 25.0 | follow-up | 0 |
6 | 70.5 | M | sigmoid | TisNxM0 | 0 | MLH1 | 78.4 | 24.5 | follow-up | 0 | ||
7 | 35.5 | M | caecum | T3N1M0 | III | MLH1 | 44.3 | 44.3 | gastric cancer | 28.0 | symptoms | 0 |
8 | 57.3 | F | sigmoid | T3N0M0 | II | MLH1 | 63.3 | 30.0 | follow-up | 0 | ||
9 | 54.5 | F | caecum | T2N0M0 | I | MLH1 | 63.4 | 63.4 | CRC | 31.2 | follow-up | 0 |
10 | 71.6 | F | rectum | T2N0M0 | I | MLH1 | 75.1 | 75.1 | biliary tract cancer | 24.0 | follow-up | 0 |
11 | 41.7 | F | descendens | T3N2M0 | III | MLH1 | 44.7 | 44.7 | CRC | 23.0 | symptoms | 0 |
12 | 43.6 | F | ascendens | T1N0M0 | I | MLH1 | 57.5 | 57.5 | breast cancer | 26.0 | follow-up | 0 |
13 | 41.7 | F | tranverse | T1N0M0 | I | MLH1 | 50.1 | 26.0 | follow-up | adenoma with LG dysplasia | ||
14 | 42.4 | F | tranverse | T3N0M0 | II | MLH1 | 48.8 | 48.8 | pancreatic cancer | 24.4 | follow-up | 0 |
15 | 71.5 | M | ascendens | T2N0M0 | I | MSH2 | 84.1 | 36.0 | follow-up | adenoma with LG dysplasia | ||
16 | 43.6 | M | tranverse | T3N0M0 | II | MLH1 | 53.9 | 53.9 | another CRC | 26.0 | follow-up | 0 |
17 | 71.9 | F | caecum | T2N0M0 | I | MLH1 | 81.4 | 81.4 | pneumonia | 29.0 | follow-up | 0 |
18 | 69.0 | F | caecum | T2N0M0 | I | MSH2 | 69.0 | 69.0 | postoperative complication | 37.7 | symptoms | 0 |
19 | 42.0 | F | caecum | T1N0M0 | I | MLH1 | 58.2 | 39.5 | follow-up | 0 | ||
20 | 35.1 | M | caecum | Dukes B | II | MLH1 | 64.4 | 37.6 | follow-up | 0 | ||
21.a | 54.2 | F | ascendens | T2N0M0 | I | MLH1 | 63.3 | 30.1 | follow-up | 0 | ||
21.b | 56.8 | F | sigmoid | T3N0M0 | II | MLH1 | 63.3 | 28.8 | follow-up | 0 | ||
22 | 54.2 | M | ascendens | T3N0M0 | II | MLH1 | 63.4 | 65.0 | CUP (brain. lung) | 18.0 | follow-up | adenoma with LG dysplasia |
23 | 53.8 | M | ascendens | T2N0M0 | I | MLH1 | 58.8 | 16.4 | follow-up | adenoma with LG dysplasia | ||
24 | 82.8 | M | descendens | T2N0M0 | I | MLH1 | 85.1 | 24.6 | follow-up | 0 | ||
25 | 55.0 | F | caecum | T1N0M0 | I | MLH1 | 66.4 | 39.1 | follow-up | 0 | ||
26 | 43.5 | M | caecum | T2N0M0 | I | MLH1 | 52.5 | 36.2 | follow-up | 0 | ||
27 | 27.2 | M | caecum | T2N0M0 | I | MLH1 | 42.9 | 37.9 | follow-up | 0 |
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Ahadova, A.; Pfuderer, P.L.; Ahtiainen, M.; Ballhausen, A.; Bohaumilitzky, L.; Kösegi, S.; Müller, N.; Tang, Y.L.; Kosmalla, K.; Witt, J.; et al. Distinct Mutational Profile of Lynch Syndrome Colorectal Cancers Diagnosed under Regular Colonoscopy Surveillance. J. Clin. Med. 2021, 10, 2458. https://doi.org/10.3390/jcm10112458
Ahadova A, Pfuderer PL, Ahtiainen M, Ballhausen A, Bohaumilitzky L, Kösegi S, Müller N, Tang YL, Kosmalla K, Witt J, et al. Distinct Mutational Profile of Lynch Syndrome Colorectal Cancers Diagnosed under Regular Colonoscopy Surveillance. Journal of Clinical Medicine. 2021; 10(11):2458. https://doi.org/10.3390/jcm10112458
Chicago/Turabian StyleAhadova, Aysel, Pauline Luise Pfuderer, Maarit Ahtiainen, Alexej Ballhausen, Lena Bohaumilitzky, Svenja Kösegi, Nico Müller, Yee Lin Tang, Kosima Kosmalla, Johannes Witt, and et al. 2021. "Distinct Mutational Profile of Lynch Syndrome Colorectal Cancers Diagnosed under Regular Colonoscopy Surveillance" Journal of Clinical Medicine 10, no. 11: 2458. https://doi.org/10.3390/jcm10112458
APA StyleAhadova, A., Pfuderer, P. L., Ahtiainen, M., Ballhausen, A., Bohaumilitzky, L., Kösegi, S., Müller, N., Tang, Y. L., Kosmalla, K., Witt, J., Endris, V., Stenzinger, A., von Knebel Doeberitz, M., Bläker, H., Renkonen-Sinisalo, L., Lepistö, A., Böhm, J., Mecklin, J. -P., Seppälä, T. T., & Kloor, M. (2021). Distinct Mutational Profile of Lynch Syndrome Colorectal Cancers Diagnosed under Regular Colonoscopy Surveillance. Journal of Clinical Medicine, 10(11), 2458. https://doi.org/10.3390/jcm10112458