The current state of molecular cytogenetics in cancer diagnosis

Abstract

Cytogenetics and molecular cytogenetics are and will continue to be indispensable tools in cancer diagnostics. Leukemia and lymphoma diagnostics are still emphases of routine (molecular) cytogenetics and corresponding studies of solid tumors gain more and more prominence. Here, first a historical perspective of molecular tumor cytogenetics is provided, which is followed by the basic principles of the fluorescence in situ hybridization (FISH) approach. Finally the current state of molecular cytogenetics in cancer diagnostics is discussed. Nowadays routine diagnostics includes basic FISH approaches rather than multicolor-FISH. The latter together with modern high-throughput methods have their impact on research to identify new tumor-associated genomic regions.

Keywords:

• copy number variation
• counseling
• cytogenetics
• fluorescence in situ hybridization
• leukemia
• lymphoma
• molecular cytogenetics
• oncogene
• solid tumors
• tumor suppressor gene

Acknowledgements

Supported in part by the DAAD and KAAD.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Key issues

• Molecular cytogenetics evolved in 1986 from cytogenetics.

• Cytogenetics started to gain major relevance in cancer diagnostics after identification of the first tumor-associated chromosomal aberration in 1960.

• Molecular cytogenetics uses different kinds of probes, such as locus-specific ones, whole and partial chromosome painting probes and probes specific for repetitive sequences.

• Two-color fluorescence in situ hybridization (FISH) is applied in routine cancer diagnostics, while multicolor FISH (mFISH) methods are applied more in research-associated settings.

• Locus-specific probes are routinely applied for the detection of tumor-suppressor gene deletion, oncogene amplification and/or gene fusions, as well as hypo- and hyperdiploidies.

• Molecular cytogenetics routine applications are used in leukemia, lymphoma and solid tumor diagnostics.

• Cytogenetics and molecular cytogenetics is single cell directed and thus able to detect even acquired low-level mosaics.

• One has to be prepared to meet also in cancer diagnostics from time to time hereditary cases, which need special attention.

• mFISH as well as array-comparative genomic hybridization and next-generation sequencing are highly suited for research settings, able to identify new tumor-relevant genetic markers.

• mFISH, array-comparative genomic hybridization and next-generation sequencing are and will in the near future be too expensive to become routine cancer diagnostic tools from a worldwide perspective.

• Cytogenetics and molecular cytogenetics are and will stay in the future indispensable tools in cancer diagnostics.

Notes

¹A ‘cytogenetic marker’ is a set phrase in tumor cytogenetics. It can be, for example, a trisomy 8 as well as a translocation leading to oncogene activation or a deletion leading to tumor-suppressor gene loss.