Abstract
Hodgkin lymphoma (HL) is one of the most common lymphomas, with an incidence of 3 per 100,000 persons. Current treatment uses a cocktail of genotoxic agents, including adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD), along with or without radiotherapy. This treatment regimen has proved to be efficient in killing cancer cells, resulting in HL patients having a survival rate of >90% cancer-free survival at five years. However, this therapy does not have a specific cell target, and it can induce damage in the genome of non-cancerous cells. Previous studies have shown that HL survivors often exhibit karyotypes characterized by complex chromosomal abnormalities that are difficult to analyze by conventional banding. Multicolor fluorescence in situ hybridization (M-FISH) is a powerful tool to analyze complex karyotypes; we used M-FISH to investigate the presence of chromosomal damage in peripheral blood lymphocytes from five healthy individuals and five HL patients before, during, and one year after anti-cancer treatment. Our results show that this anti-cancer treatment-induced genomic chaos that persists in the hematopoietic stem cells from HL patients one year after finishing therapy. This chromosomal instability may play a role in the occurrence of second primary cancers that are observed in 10% of HL survivors. This chapter will describe a protocol for utilizing M-FISH to study treatment-induced genome chaos in Hodgkin’s lymphoma (HL) patients, following a brief discussion.
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References
Küppers R, Engert A, Hansmann M (2012) Review series Hodgkin lymphoma. J Clin Invest 122:3439–3447
Ansell SM (2015) Hodgkin lymphoma: diagnosis and treatment. Mayo Clin Proc 90:1574–1583
Marr KC, Connors JM, Savage KJ, Goddard KJ, Deyel RJ (2017) ABVD chemotherapy with reduced radiation therapy rates in children, adolescents and young adults with all stages of Hodgkin lymphoma. Ann Oncol 28:849–854
Witt KL, Bishop JB (1996) Mutagenicity of anticancer drugs in mammalian germ cells. Mutat Res Mol Mech Mutagen 355:209–234
Weber GF (2015) DNA damaging drugs. Molecular therapies of cancer. Springer, pp 9–112. https://doi.org/10.1007/978-3-319-13278-5
Zahnreich S, Schmidberger H (2021) Childhood cancer: occurrence, treatment and risk of second primary malignancies. Cancers (Basel) 13
Bilban-Jakopin C, Bilban M (2001) Genotoxic effects of radiotherapy and chemotherapy on circulating lymphocytes in patients with Hodgkin’s disease. Mutat Res Genet Toxicol Environ Mutagen 497:81–88
M’kacher R et al (2003) Baseline and treatment-induced chromosomal abnormalities in peripheral blood lymphocytes of Hodgkin’s lymphoma patients. Int J Radiat Oncol Biol Phys 57:321–326
Salas C et al (2012) Persistent genomic instability in peripheral blood lymphocytes from hodgkin lymphoma survivors. Environ Mol Mutagen 53:271–280
Ramos S et al (2018) Genomic chaos in peripheral blood lymphocytes of Hodgkin’s lymphoma patients one year after ABVD chemotherapy/radiotherapy. Environ Mol Mutagen 59:755–768
Frias S et al (2003) NOVP chemotherapy for Hodgkin’s disease transiently induces sperm aneuploidies associated with the major clinical aneuploidy syndromes involving chromosomes X, Y, 18, and 21. Cancer Res 63:44–51
Frias S, Van Hummelen P, Meistrich ML, Wyrobek AJ (2021) Meiotic susceptibility for induction of sperm with chromosomal aberrations in patients receiving combination chemotherapy for Hodgkin lymphoma. PLoS One 15:1–19
de Vries S et al (2021) Long-term cause-specific mortality in Hodgkin lymphoma patients. J Natl Cancer Inst 113:760–769
Smith LM, Evans JW, Mori M, Brown M (1992) The frequency of translocations after treatment for Hodgkin’s disease. Int J Radiat Oncol Biol Phys 24:737–742
Heng J, Heng HH (2022) Genome chaos, information creation, and cancer emergence: searching for new frameworks on the 50th anniversary of the “war on cancer”. Genes (Basel) 13
Geigl JB, Uhrig S, Speicher MR (2006) Multiplex-fluorescence in situ hybridization for chromosome karyoty**. Nat Protoc 1:1172–1184
Frias S et al (2019) Nonclonal chromosome aberrations and genome chaos in somatic and germ cells from patients and survivors of Hodgkin lymphoma. Genes (Basel) 10:37
Heng HHQ, Regan SM, Liu G, Ye CJ (2016) Why it is crucial to analyze non clonal chromosome aberrations or NCCAs? Mol Cytogenet 9:1–12
Rangel N, Forero-Castro M, Rondón-Lagos M (2017) New insights in the cytogenetic practice: Karyotypic chaos, non-clonal chromosomal alterations and chromosomal instability in human cancer and therapy response. Genes (Basel) 8:2–29
Heng J, Heng HH (2021) Two-phased evolution: genome chaos-mediated information creation and maintenance. Prog Biophys Mol Biol 165:29–42
Salas C, Pérez-Vera P, Frías S (2011) Genetic abnormalities in leukemia secondary to treatment in patients with Hodgkin’s disease. Revista de Investigacion Clinica 63:53–63
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Ramos, S., Frias, S. (2024). Characterizing Chemotherapy/Radiotherapy-Induced Genome Chaos in Hodgkin’s Lymphoma Patients Using M-FISH. In: Ye, J.C., Heng, H.H. (eds) Cancer Cytogenetics and Cytogenomics. Methods in Molecular Biology, vol 2825. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3946-7_14
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DOI: https://doi.org/10.1007/978-1-0716-3946-7_14
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