Ann Lab Med.  2014 Nov;34(6):413-425. 10.3343/alm.2014.34.6.413.

Cancer Cytogenetics: Methodology Revisited

• Wan TS

• KMID: 2129566
• DOI: http://doi.org/10.3343/alm.2014.34.6.413

Abstract

The Philadelphia chromosome was the first genetic abnormality discovered in cancer (in 1960), and it was found to be consistently associated with CML. The description of the Philadelphia chromosome ushered in a new era in the field of cancer cytogenetics. Accumulating genetic data have been shown to be intimately associated with the diagnosis and prognosis of neoplasms; thus, karyotyping is now considered a mandatory investigation for all newly diagnosed leukemias. The development of FISH in the 1980s overcame many of the drawbacks of assessing the genetic alterations in cancer cells by karyotyping. Karyotyping of cancer cells remains the gold standard since it provides a global analysis of the abnormalities in the entire genome of a single cell. However, subsequent methodological advances in molecular cytogenetics based on the principle of FISH that were initiated in the early 1990s have greatly enhanced the efficiency and accuracy of karyotype analysis by marrying conventional cytogenetics with molecular technologies. In this review, the development, current utilization, and technical pitfalls of both the conventional and molecular cytogenetics approaches used for cancer diagnosis over the past five decades will be discussed.

Keyword

Cancer cytogenetics; FISH; Karyotyping; Molecular cytogenetics

MeSH Terms

Chromosome Aberrations
Humans
In Situ Hybridization, Fluorescence
Karyotyping
Leukemia/diagnosis/genetics/pathology
Neoplasms/*diagnosis/genetics/pathology
Prognosis

Figure

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  Fig. 1 Protocol for the preparation of a karyotype from a leukemic patient.

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  Fig. 2 Partial karyotype showing normal variants and chromosome abnormalities of leukemia. (A) Normal variant with 1qh+ (arrow), (B) Normal variant with inv(9)(p11q13) (arrow), (C) dup(1)(q21q32) chromosome with duplication of a 1q21-q32 chromosomal fragment (arrow), (D) trp(1)(q21q32) chromosome with triplication of a 1q21-q32 chromosomal fragment (arrow), (E) del(7)(q) chromosome with terminal deletion ofa7q22-qter chromosomal fragment (arrow), (F) del(5)(q13q33) chromosome with an interstitial deletion of a 5q13-q33 chromosomal fragment (arrow), (G) der(1)t(1;1)(p35;q25) chromosome with loss of a 1p35-pter chromosomal fragment and duplication of a 1q25-qter chromosomal fragment (arrow), (H) i(17)(q10) chromosome with a loss of the whole short arm and duplication of the whole long of chromosome 17 (arrow), (I) t(9;22)(q34;q11.2), a balanced translocation between 9q34 and 22q11.2 (arrows), (J) t(2;9;22)(q37;q34;q11.2), a balanced three-way translocation between 2q37, 9q34, and 22q11.2 (arrows), (K) der(1;7)(q10;p10), a centric fusion of the whole arms of 1q and 7p with a gain of 1q and a loss of 7q (arrow), (L) der(5)ins(5;?)(q13;?) chromosome with an unknown chromosomal fragment inserted into 5q13 (arrow), (M) inv(16)(p13q22) chromosome with G-banding (arrow), (N) inv(16)(p13q22) chromosome with R-banding (arrow).

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  Fig. 3 FISH protocol. It includes sample pretreatment, denaturation of probe and sample, hybridization, post-hybridization washing, and fluorescent signal detection.

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  Fig. 4 Interphase FISH images. (A) Interphase FISH using dual color centromeric-specific probes for chromosomes X (red) and Y (green) to determine the proportion of donor cells in the peripheral blood of the recipient (XY, arrow; XX, block arrow). (B) Interphase FISH using a dual color dual fusion BCR-ABL1 translocation probe, showing a 2G2R pattern in a normal cell (block arrow) and 1G1R2F in a Philadelphia-positive cell (arrow). (C) Interphase FISH using a dual color breakapart MLL translocation probe, showing an MLL split signal (distal MLL region, arrow; proximal MLL region, block arrow), and indicating MLL gene rearrangement. (D) MYC amplification in a neuroblastoma (arrow) and a normal cell with a 2G2R pattern (block arrow). The MYCN gene is labeled with a green fluorochrome, whereas the centromeric probe for chromosome 2 is labeled with a red fluorochrome.

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