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Cancers develop from the acquisition of somatic alterations, combined with germline genetic, lifestyle, and environmental risk factors. The type of germline genetic mutation can influence the acquisition of cancer-driving point mutations and chromosomal rearrangements. For many years, pathologists and clinicians have used cytogenetic analysis as a powerful tool for the diagnosis and classification of malignant hematologic diseases. In the modern era, germline genetic risk is evaluated alongside acquired cytogenetic and molecular changes. Importantly, especially for individuals with a germline predisposition to hematopoietic malignancies, the detection of an acquired, recurrent cytogenetic abnormality establishes the diagnosis of a neoplastic disorder, provides prognostic information, and rules out hyperplasia, dysplasia, or morphological changes caused by a germline mutation or environmental factor, such as toxic injury or vitamin deficiency. Specific cytogenetic abnormalities have been identified that are very closely, and sometimes uniquely, associated with morphologically distinct subsets of leukemia or lymphoma, enabling clinicians to predict their clinical course and likelihood of responding to particular treatments. In many cases, the prognostic information derived from cytogenetic analysis is independent of that provided by other clinical features. Patients with favorable prognostic features benefit from standard therapies with a well-known spectra of toxicities, whereas those with less favorable clinical and cytogenetic characteristics may be better treated with more intensive or investigational therapies. Pretreatment cytogenetic analysis also can be useful in choosing between postremission therapies that differ widely in cost, acute and chronic morbidity, and effectiveness. The appearance of new abnormalities in the karyotype of a patient under observation often signals clonal evolution and more aggressive behavior. The disappearance of a chromosomal abnormality present at diagnosis is an important indicator of complete remission after treatment, and its reappearance may herald disease recurrence.

Acronyms and Abbreviations

ALL, acute lymphocytic or lymphoblastic leukemia; AML, acute myeloid leukemia; CML, chronic myeloid leukemia; CLL, chronic lymphocytic leukemia; DLBCL, diffuse large B-cell lymphoma; del, deletion; EBV, Epstein Barr virus; FISH, fluorescence in situ hybridization; IGH, immunoglobulin heavy chain; inv, inversion; LOH, loss of heterozygosity; MDS, myelodysplastic syndrome; NHL, non-Hodgkin lymphoma; Ph, Philadelphia chromosome, qRT-PCR, quantitative reverse transcriptase polymerase chain reaction; RA, refractory anemia, RARS, refractory anemia with ring sideroblasts; RCMD, refractory cytopenia with multilineage dysplasia; RAEB, refractory anemia with excess blasts; SKY, spectral karyotyping; SNP, single nucleotide polymorphism, t, translocation; t-, therapy-related, TKI – tyrosine kinase inhibitor.


Cancers develop from the interplay of inherent cancer risk associated with germline genetic variants and acquired somatic chromosomal rearrangements and gene mutations, as well as behavioral and environmental risk factors. In some cases, it is easy to surmise the risk associated with germline mutations, as exemplified by the high risk of myeloid leukemias in people with germline CEBPA mutations at the 5′ end of the gene.1 In others, a combined effect of both germline genetic risk with environmental exposure likely contributes to the development of malignancy. For example, 20% ...

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