The Principles of Clinical Cytogenetics - Extra Materials - Springer

Cytogenetics of Solid Tumors 421
INTRODUCTION
From: The Principles of Clinical Cytogenetics, Second Edition
Edited by: S. L. Gersen and M. B. Keagle © Humana Press Inc., Totowa, NJ
421
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Cytogenetics of Solid Tumors
Jonathan A. Fletcher, MD
The field of cytogenetics has had a great impact on clinical and basic sciences in hematology and
oncology, and both karyotyping and fluorescence in situ hybridization (FISH) assays are of growing
relevance in solid tumor oncology. Although most of the cancer cytogenetic work in clinical laboratories
is directed to hematological disorders, it is increasingly evident that cytogenetic assays are essential
in providing diagnostic or prognostic information for various solid tumors (see Tables 1 and 2).
However, several aspects of the cytogenetic approach present unique challenges in solid tumors.
Whereas hematological neoplasms can be sampled by minimally invasive methods, such as bone
marrow aspiration or, sometimes, even phlebotomy, solid tumors are generally karyotyped using
specimens obtained by open biopsy. Therefore, solid-tumor cytogenetic analyses are typically performed
at the time of initial diagnosis or when the tumor is rebiopsied at the time of clinical progression,
but they are not performed routinely to monitor treatment response in a given patient. In contrast,
hematologic cytogenetic analyses are often repeated at regular intervals in a given patient, so as to
monitor disease activity. Another difference between hematological and solid-tumor cytogenetics is
that solid-tumor karyotypes are often extremely complex, particularly those in highly malignant solid
tumors. A single metaphase cell might contain dozens of clonal and nonclonal chromosomal aberrations,
and in such tumors, it is impractical to characterize the exact mechanisms of rearrangement
responsible for each chromosomal aberration, particularly in the course of a routine clinical analysis.
A final difference is that the solid-tumor sample generally must be disaggregated by mechanical and
enzymatic methods before the cells are placed in tissue culture.
Although solid tumors are less readily accessible to biopsy compared to hematological neoplasms,
it is increasingly common to sample solid tumors by fine-needle percutaneous approaches. Needle
sampling is often performed under ultrasound or computed tomography (CT) guidance and can involve
taking a fine-needle aspirate or needle core biopsy from the tumor. Solid tumor samples obtained by
these methods can be karyotyped successfully (1–4), but the small amount of starting material is a
constraint in that fewer cultures can be established. FISH analyses, on the other hand, are straightforward
in fine-needle specimens (5,6).
Since the mid-1980s, various advances in tumor cell culture, including the use of collagenase for
cell disaggregation (7), have enabled more routine cytogenetic analysis of solid tumors. Nonrandom
chromosomal abnormalities have been described in many varieties of solid tumors, and many of
these are diagnostically or prognostically relevant (see Tables 1 and 2). Increasingly, the methods
used for these analyses have become standardized between different clinical laboratories, although
there remain many variations of the basic methods. Irrespective of the particular methods used, there
are many general considerations that influence the success of tumor cytogenetic analyses.