Genetic heterogeneity in lung and colorectal carcinoma as revealed by microsatellite analysis in plasma or tumor tissue DNA.
BACKGROUND
Determination of tumor clonality has implications for molecular characterization and the optimal treatment of cancer. Allelotyping allows detection of the two alleles, maternal and paternal, and provides additional information regarding clonal genetic defects. The presence of allelic imbalances (AI) in tumors is a general event, but is not necessary at the same allele (alternative AI). The authors' goal was to determine whether the presence of alternative AI (AA) was a marker of heterogeneity and prognosis.


METHODS
To further analyze the heterogeneity of lung tumors, tumor DNA released in the plasma was compared with primary tumor DNA from 24 lung carcinoma patients. The comparison was performed by allelotyping using 12 microsatellites targeting 9 chromosomal regions, taking in each case leukocyte DNA as reference. To extend and confirm these observations, 26 primary colorectal carcinomas with paired synchronous liver metastasis were analyzed using an enlarged panel of 33 microsatellites.


RESULTS
AA were observed in 40% (20 of 50) of all patients, in 25% (6 of 24) of lung carcinoma patients but at a higher level, and in 54% (14 of 26) of colorectal carcinoma patients. They affected different chromosome localizations and each tumor stage. In both types of cancer, patients with AA had a higher AI mean frequency in their primary tumor.


CONCLUSIONS
Detection of AA is an original marker of heterogeneous tumors, demonstrating that independent events occurred on specific genetic sites required for cancer progression.
Beau-Faller
Michèle
M
Laboratoire de Biochimie et de Biologie Moléculaire, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, Strasbourg, France. mariepierre.gaub@chru-strasbourg.fr
Weber
Jean-Christophe
JC
Schneider
Anne
A
Guèrin
Eric
E
Gasser
Bernard
B
Ducrocq
Xavier
X
Jaeck
Daniel
D
Wihlm
Jean-Marie
JM
Quoix
Elisabeth
E
Gaub
Marie-Pierre
MP
D000230:Adenocarcinoma / Q000097:blood / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D022981:Allelic Imbalance; D018288:Carcinoma, Small Cell / Q000097:blood / Q000235:genetics* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000235:genetics* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D018740:Genetic Heterogeneity; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011379:Prognosis
D004273:DNA, Neoplasm