Chromothripsis in Oncology: Literature Review and Case Report

Abstract

The article presents a clinical case and literature review dwelling on the recently discovered chromothripsis phenomenon in oncology. Chromothripsis is a type of complex genome changes when a chromosome is first torn into dozens and even thousands of fragments, and then these fragments are bound in a random manner. Sometimes, several chromosomes are involved in the restructuring. As a result, genome mutant zones are formed which trigger malignancies and congenital diseases. In other words, the use of certain methodological approaches (multicolor fluorescence in situ hybridization, SKY technique, and some others) permits to observe under a microscope the splitting of two or more chromosomes and further reunification of these fragments into new unusual two- or multicolor structures, chromosomal markers. Chromothripsis is a rare phenomenon with a peculiar pattern observed in clones of cells of various tumors including hematopoietic and lymphoid tissue malignancies. There are published data on a higher incidence of this phenomenon in patients with myelodysplastic syndromes and bone tumors. TP53 gene mutations play an important role in the development of chromothripsis. The use of paired-sequencing DNA or SNP approaches in oncology is promising both in theoretical and clinical application. The first subject cohort should include patients with TP53 and MLL gene mutations, complex chromosomal aberrations, EVI-1 gene overexpression, and some others. The article presents the chromothripsis phenomenon in an 8-month-old girl with M7 acute myeloid leukemia.

Chromothripsis—Explosion in Genetic Science

“…So in a recent study, it was found that chromothripsis was detected in 100% cases of malignant tumors of the peripheral nerve sheath, and in 71% cases of germ cell tumors [ 48 ]. Chromothripsis is regularly found in blood cancer, cancer of the central nervous system, in soft tissue tumors and carcinomas [ 49 , 50 ], in osteosarcoma and glioblastoma [ 8 , 51 , 52 , 53 , 54 , 55 ]. It was found that the incidence of chromothripsis in cancer is significantly higher in patients with hereditary genetic disorders associated with gene mutations in the cell cycle and DNA repair [ 56 , 57 ].…”