Chromosome, Microdissection and Microcloning
51
Tab. 2
Disease-specifc chromosomal regions mapped by
microdissection methods.
Disease
Chromosomal region
Adenocarcinoma oF the lung
9q, 16p
Acute myelogenous leukemia (ETO gene)
8q22
Autism/mental retardation
4q21
Basal cell carcinoma
9q22.3
Cervical carcinoma
6p21.3
Colorectal carcinoma
5q, 18q
Congenital heart deFect
6p22.1–6pter
Ductal carcinoma breast
11q22–q23
Esophageal adenocarcinoma
4q32–33
Glioma
10q23.3
Melanoma
10q24–25
Ovarian cancer primary
3q25–q26
Ovarian cancer metastatic
3p25–p26
Pancreatic carcinoid
8p12–22
Prostate carcinoma
16q
Psychomotor/growth retardation
13q22–q32, 5q31.3q33.3
Small-cell lung carcinoma
3q13.2
Urinary bladder carcinoma (EG±R gene)
7p11–p12
sample of the numerous lesions/diseases
for which chromosomal aberrations have
been mapped by various microdissection
techniques. In some instances, a speciFc
gene has been identiFed as being po-
tentially involved in the etiology of the
disease. In other instances inactivation
or absence of tumor suppressor genes
are being sought as the cause of the
disease.
How is functional genomics likely to
impact on the pathology laboratory? Im-
portant aspects of functional genomics in
the post genome era include the LCM,
DNA and cDNA microarrays, proteomic
methods, collaborative human tissue bank-
ing, tissue microarrays, and pathobioin-
forma
t
ics
.Thero
leo
fmassspec
troscopy
in the analysis of RNA, DNA, and pro-
tein has expanded. The recent combina-
tion of LCM and high-throughput cDNA
microarrays provides a unique opportu-
nity to generate gene expression proFles
of cells from various stages of tumor
progression as it occurs in the actual
neoplastic tissue milieu. This combina-
tion was put to use to monitor
in vivo
gene expression levels in puriFed normal,
invasive, and metastatic breast cell pop-
ulations from a single patient. Expression
proFles were veriFed by real-time quantita-
tive PCR and immunohistochemistry and
were proven to be generally applicable to
the study of progression of malignancy.
Rubin has used LCM, cDNA microar-
rays, and tissue microarrays to validate
the presence of differentially expressed
genes in various stages of prostate can-
cer. Pasinetti et al. conducted a large-scale
gene expression proFling study using LCM
and a number of tumors and their nor-
mal counterparts (e.g. tumor and normal
oral epithelium). About 600 genes were
found to be associated with oral can-
cer. These included oncogenes, tumor
suppressor genes, transcription factors,
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