c h a p t e r
Basic Cytogenetics and the Role of Genetics
in Cancer Development
Alain Verhest and pierre Heimann
In tro d u c tio n
A c q u ire d C h ro m o s o m a l A b e rra tio n s in C a n c e r
H isto ric a l B a c k g ro u n d
I n t r o d u c t io n
B a sic K n o w le d g e o f C y to g e n e tic s
L y m p h o m a s
C e ll C y c le
T h y r o id C a rc in o m a s
T h e I n te rp h a s e
C lin ic a l A p p lic a tio n s o f C o n v e n tio n a l C y t o g e n e tic s a n d F IsH
T h e M ito s is
in C y t o lo g y
T h e M e io s is
t h e C h r o m o s o m e S t r u c t u r e
I n t r o d u c t io n
M e th o d o lo g y
a p p lic a t io n
T h e K a r y o ty p e
C o n c lu d in g R e m a rk s
F lu o r e s c e n t in S itu H y b r id iz a tio n
C o m p a r a t iv e G e n o m ic H y b r id iz a tio n (C G H )
This chapter will summarize the knowledge acquired on con-
ventional cancer cytogenetics in the second half of the last
century and introduces additional applications of fluorescent in
situ hybridization available for the study of cancer development
and evolution.
Other indications of these techniques applied on cytology
samples are also described in Chapter 36.
Historical Background
As suspected by von Hansemann more than a century ago, can-
cers are associated with nuclear and mitotic anomalies in their
In 1914, Boveri hypothesized his theory on somatic mutations
responsible for the origin and development of malignant trans-
formation. He stressed the acquisition of an unbalanced chro-
mosome constitution as a cause of cancer illustrated by mitotic
asymmetry and asynchrony, and foresaw the monoclonal ori-
gin of the cancer cell. It took at least 40 more years to establish
the exact number of human chromosomes. The blood-culturing
method became more successful than the squash method when
colcemid was discovered to arrest the mitotic cycle in metaphase
by poisoning the mitotic spindle and to prevent the centromeres
from dividing. The erroneous adjunction of a hypotonic solu-
tion to a pellet of harvested cells was an unexpected improve-
ment in the spread of individualized chromosomes rid of their
cellular envelope, resulting in a nicer dispersal on the metaphase
In 1956 Tjio and Levan accurately reported that the
human somatic cell contains 46 chromosomes, including
22 pairs of autosomes and one pair of sex chromosomes;
one X of maternal origin and the other chromosome—X or
Y—being from the paternal source.1
Rarely have discoveries
had such impact on modern biology and medicine as the
description of the 46-chromosome karyotype. The newborn
cytogenetic discipline investigated simultaneously the field
of inherited diseases and acquired chromosomal anomalies
in cancer cells.
Trisomies of chromosome 21 in mongolism and of other
autosomes or numerical variations of sex chromosomes proved
their specificity and consequently their diagnostic value in con-
genital syndromes. In 1960 Nowell and Hungerford reported
the first evidence of a chromosome anomaly specifically associ-
ated with a malignant disease, the chronic myelogenous leuke-
mia.2 They showed the recurrent presence in leukemic leukocytes
of a deleted small chromosome that they named the Philadel-
phia (Ph) chromosome in reference to the city where they were
working. This proof of a genetic cause in cancer was the starting
point to new insights into the pathways of malignant initiation
and progression.
Basic Knowledge of Cytogenetics
The human somatic cell contains two copies of each chromo-
some, one from paternal and the other from maternal origin.
Therefore the karyotype is diploid with doubled amount of
deoxyribonucleic acid (DNA)
compared to the gametes (n)
with a single set of 23 chromosomes.
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