Clonal Hematopoiesis and Liquid Biopsy in Gastrointestinal Cancers

Vlad M Croitoru, Irina M Cazacu, Ionut Popescu, Doru Paul, Simona Olimpia Dima, Adina Emilia Croitoru, Alina Daniela Tanase, Vlad M Croitoru, Irina M Cazacu, Ionut Popescu, Doru Paul, Simona Olimpia Dima, Adina Emilia Croitoru, Alina Daniela Tanase

Abstract

The use of blood liquid biopsy is increasingly being incorporated into the clinical setting of gastrointestinal cancers care. Clonal hematopoiesis (CH) occurs naturally as a result of the accumulation of somatic mutations and the clonal proliferation of hematopoietic stem cells with normal aging. The identification of CH-mutations has been described as a source of biological noise in blood liquid biopsy. Incorrect interpretation of CH events as cancer related can have a direct impact on cancer diagnosis and treatment. This review summarizes the current understanding of CH as a form of biological noise in blood liquid biopsy and the reported clinical significance of CH in patients with GI cancers.

Keywords: cancer; cfDNA; clonal hematopoiesis; gastrointestinal tumor; liquid biopsy.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Croitoru, Cazacu, Popescu, Paul, Dima, Croitoru and Tanase.

Figures

Figure 1
Figure 1
Summary of the genes with CH and tumor-related mutations found in the studies included in the review. (A) Leal et al. (28); (B) Chan et al. (32); (C) Huang et al. (33); (D) Ococks et al. (35).
Figure 2
Figure 2
Targeted sequencing of paired cfDNA and white blood cells to correctly asses the origin of the mutations.

References

    1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. . Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. (2021) 71:209–49. 10.3322/caac.21660
    1. Heitzer E, Haque IS, Roberts CES, Speicher MR. Current and future perspectives of liquid biopsies in genomics-driven oncology. Nat Rev Genet. (2019) 20:71–88. 10.1038/s41576-018-0071-5
    1. Saini A, Pershad Y, Albadawi H, Kuo M, Alzubaidi S, Naidu S, et al. . Liquid biopsy in gastrointestinal cancers. Diagnostics. (2018) 8:75. 10.3390/diagnostics8040075
    1. Fici P. Cell-free DNA in the liquid biopsy context: role and differences between ctDNA and CTC marker in cancer management. Methods Mol Biol. (2019) 1909:47–73. 10.1007/978-1-4939-8973-7_4
    1. Bellosillo B, Montagut C. High-accuracy liquid biopsies. Nat Med. (2019) 25:1820–1. 10.1038/s41591-019-0690-1
    1. Chan HT, Chin YM, Nakamura Y, Low SK. Clonal hematopoiesis in liquid biopsy: From biological noise to valuable clinical implications. Cancers. (2020) 12:1–18. 10.3390/cancers12082277
    1. Jaiswal S, Fontanillas P, Flannick J, Manning A, Grauman PV, Mar BG, et al. . Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med. (2014) 371:2488–98. 10.1056/NEJMoa1408617
    1. von Bonin M, Jambor HK, Teipel R, Stölzel F, Thiede C, Damm F, et al. . Clonal hematopoiesis and its emerging effects on cellular therapies. Leukemia. (2021) 35:2752–8. 10.1038/s41375-021-01337-8
    1. Hu Y, Ulrich BC, Supplee J, Kuang Y, Lizotte PH, Feeney NB, et al. . False-positive plasma genotyping due to clonal hematopoiesis. Clin Cancer Res. (2018) 24:4437–43. 10.1158/1078-0432.CCR-18-0143
    1. Acuna-Hidalgo R, Sengul H, Steehouwer M, van de Vorst M, Vermeulen SH, Kiemeney L, et al. . Ultra-sensitive sequencing identifies high prevalence of clonal hematopoiesis-associated mutations throughout adult life. Am J Hum Genet. (2017) 101:50–64. 10.1016/j.ajhg.2017.05.013
    1. Ptashkin RN, Mandelker DL, Coombs CC, Bolton K, Yelskaya Z, Hyman DM, et al. . Prevalence of clonal hematopoiesis mutations in tumor-only clinical genomic profiling of solid tumors. JAMA Oncology. (2018) 4:1589–93. 10.1001/jamaoncol.2018.2297
    1. Buscarlet M, Provost S, Zada YF, Bourgoin V, Mollica L, Dubé M-P, et al. . Lineage restriction analyses in CHIP indicate myeloid bias for TET2 and multipotent stem cell origin for DNMT3A. Blood. (2018) 132:277–80. 10.1182/blood-2018-01-829937
    1. Arends CM, Galan-Sousa J, Hoyer K, Chan W, Jäger M, Yoshida K, et al. . Hematopoietic lineage distribution and evolutionary dynamics of clonal hematopoiesis. Leukemia. (2018) 32:1908–19. 10.1038/s41375-018-0047-7
    1. Jin P, Kang Q, Wang X, Yang L, Yu Y, Li N, et al. . Performance of a second-generation methylated SEPT9 test in detecting colorectal neoplasm. J Gastroenterol Hepatol. (2015) 30:830–3. 10.1111/jgh.12855
    1. Cohen JD, Li L, Wang Y, Thoburn C, Afsari B, Danilova L, et al. . Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science. (2018) 359:926–30. 10.1126/science.aar3247
    1. Tie J, Wang Y, Tomasetti C, Li L, Springer S, Kinde I, et al. . Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. Sci Transl Med. (2016) 8:346ra92. 10.1126/scitranslmed.aaf6219
    1. Khakoo S, Georgiou A, Gerlinger M, Cunningham D, Starling N. Circulating tumour DNA, a promising biomarker for the management of colorectal cancer. Crit Rev Oncol Hematol. (2018) 122:72–82. 10.1016/j.critrevonc.2017.12.002
    1. Tjensvoll K, Lapin M, Buhl T, Oltedal S, Steen-Ottosen Berry K, Gilje B, et al. . Clinical relevance of circulating KRAS mutated DNA in plasma from patients with advanced pancreatic cancer. Mol Oncol. (2016) 10:635–43. 10.1016/j.molonc.2015.11.012
    1. Yamauchi M, Urabe Y, Ono A, Miki D, Ochi H, Chayama K. Serial profiling of circulating tumor DNA for optimization of anti-VEGF chemotherapy in metastatic colorectal cancer patients. Int J Cancer. (2018) 142:1418–26. 10.1002/ijc.31154
    1. Overman MJ, Vauthey J-N, Aloia TA, Conrad C, Chun YS, Pereira AAL, et al. . Circulating tumor DNA (ctDNA) utilizing a high-sensitivity panel to detect minimal residual disease post liver hepatectomy and predict disease recurrence. J Clin Oncol. (2017) 35:3522. 10.1200/JCO.2017.35.15_suppl.3522
    1. Yao J, Zang W, Ge Y, Weygant N, Yu P, Li L, et al. . RAS/BRAF circulating tumor DNA mutations as a predictor of response to first-line chemotherapy in metastatic colorectal cancer patients. Can J Gastroenterol Hepatol. (2018) 2018:4248971. 10.1155/2018/4248971
    1. Garlan F, Laurent-Puig P, Sefrioui D, Siauve N, Didelot A, Sarafan-Vasseur N, et al. . Early evaluation of circulating tumor DNA as marker of therapeutic efficacy in metastatic colorectal cancer patients (PLACOL Study). Clin Cancer Res. (2017) 23:5416–25. 10.1158/1078-0432.CCR-16-3155
    1. Siravegna G, Mussolin B, Buscarino M, Corti G, Cassingena A, Crisafulli G, et al. . Clonal evolution and resistance to EGFR blockade in the blood of colorectal cancer patients. Nat Med. (2015) 21:795–801. 10.1038/nm.3870
    1. Mohan S, Heitzer E, Ulz P, Lafer I, Lax S, Auer M, et al. . Changes in colorectal carcinoma genomes under anti-EGFR therapy identified by whole-genome plasma DNA sequencing. PLoS Genet. (2014) 10:e1004271. 10.1371/journal.pgen.1004271
    1. Marass F, Stephens D, Ptashkin R, Zehir A, Berger MF, Solit DB, et al. . Fragment size analysis may distinguish clonal hematopoiesis from tumor-derived mutations in cell-free DNA. Clinical chemistry. (2020) 66:616–8. 10.1093/clinchem/hvaa026
    1. Fernandez-Cuesta L, Perdomo S, Avogbe PH, Leblay N, Delhomme TM, Gaborieau V, et al. . Identification of circulating tumor DNA for the early detection of small-cell lung cancer. EBioMedicine. (2016) 10:117–23. 10.1016/j.ebiom.2016.06.032
    1. Razavi P, Li BT, Brown DN, Jung B, Hubbell E, Shen R, et al. . High-intensity sequencing reveals the sources of plasma circulating cell-free DNA variants. Nat Med. (2019) 25:1928–37. 10.1038/s41591-019-0652-7
    1. Leal A, van Grieken NCT, Palsgrove DN, Phallen J, Medina JE, Hruban C, et al. . White blood cell and cell-free DNA analyses for detection of residual disease in gastric cancer. Nat Commun. (2020) 11:525. 10.1038/s41467-020-14310-3
    1. Jensen K, Konnick EQ, Schweizer MT, Sokolova AO, Grivas P, Cheng HH, et al. . Association of clonal hematopoiesis in DNA repair genes with prostate cancer plasma cell-free DNA testing interference. JAMA Oncology. (2021) 7:107–10. 10.1001/jamaoncol.2020.5161
    1. Schøler LV, Reinert T, Ørntoft MW, Kassentoft CG, Árnadóttir SS, Vang S, Nordentoft I, Knudsen M, et al. . Clinical implications of monitoring circulating tumor DNA in patients with colorectal cancer. Clin Cancer Res. (2017) 23:5437–45. 10.1158/1078-0432.CCR-17-0510
    1. Ng SB, Chua C, Ng M, Gan A, Poon PS, Teo M, et al. . Individualised multiplexed circulating tumour DNA assays for monitoring of tumour presence in patients after colorectal cancer surgery. Scientific reports. (2017) 7:40737. 10.1038/srep40737
    1. Chan HT, Nagayama S, Chin YM, Otaki M, Hayashi R, Kiyotani K, et al. . Clinical significance of clonal hematopoiesis in the interpretation of blood liquid biopsy. Molecular oncology. (2020) 14:1719–30. 10.1002/1878-0261.12727
    1. Huang F, Yang Y, Chen X, Jiang H, Wang H, Shen M, et al. . Chemotherapy-associated clonal hematopoiesis mutations should be taken seriously in plasma cell-free DNA KRAS/NRAS/BRAF genotyping for metastatic colorectal cancer. Clin Biochem. (2021) 92:46–53. 10.1016/j.clinbiochem.2021.03.005
    1. Maron SB, Chase LM, Lomnicki S, Kochanny S, Moore KL, Joshi SS, et al. . Circulating tumor DNA sequencing analysis of gastroesophageal adenocarcinoma. Clin Cancer Res. (2019) 25:7098–112. 10.1158/1078-0432.CCR-19-1704
    1. Ococks E, Frankell AM, Masque Soler N, Grehan N, Northrop A, Coles H, et al. . Longitudinal tracking of 97 esophageal adenocarcinomas using liquid biopsy sampling. Ann Oncol. (2021) 32:522–32. 10.1016/j.annonc.2020.12.010
    1. Coombs CC, Zehir A, Devlin SM, Kishtagari A, Syed A, Jonsson P, et al. . Therapy-related clonal hematopoiesis in patients with non-hematologic cancers is common and associated with adverse clinical outcomes. Cell Stem Cell. (2017) 21:374–82.e4. 10.1016/j.stem.2017.07.010
    1. Park SJ, Bejar R. Clonal hematopoiesis in cancer. Exp Hematol. (2020) 83:105–12. 10.1016/j.exphem.2020.02.001
    1. Jaiswal S, Natarajan P, Silver AJ, Gibson CJ, Bick AG, Shvartz E, et al. . Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease. N Engl J Med. (2017) 377:111–21. 10.1056/NEJMoa1701719
    1. Bolton KL, Ptashkin RN, Gao T, Braunstein L, Devlin SM, Kelly D, et al. . Cancer therapy shapes the fitness landscape of clonal hematopoiesis. Nature Genetics. (2020) 52:1219–26. 10.1038/s41588-020-00710-0
    1. Arends CM, Weiss M, Christen F, Eulenberg-Gustavus C, Rousselle A, Kettritz R, et al. . Clonal hematopoiesis in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis. Haematologica. (2020) 105:e264–e7. 10.3324/haematol.2019.223305
    1. Dharan NJ, Yeh P, Bloch M, Yeung MM, Baker D, Guinto J, et al. . HIV is associated with an increased risk of age-related clonal hematopoiesis among older adults. Nat Med. (2021) 27:1006–11. 10.1038/s41591-021-01357-y
    1. Bolton KL, Koh Y, Foote MB, Im H, Jee J, Sun CH, et al. . Clonal hematopoiesis is associated with risk of severe Covid-19. Nat Commun. (2021) 12:5975. 10.1038/s41467-021-26138-6
    1. Furer N, Kaushansky N, Shlush LI. The vicious and virtuous circles of clonal hematopoiesis. Nat Med. (2021) 27:949–50. 10.1038/s41591-021-01396-5
    1. Chabon JJ, Hamilton EG, Kurtz DM, Esfahani MS, Moding EJ, Stehr H, et al. . Integrating genomic features for non-invasive early lung cancer detection. Nature. (2020) 580:245–51. 10.1038/s41586-020-2140-0

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel