title: Genetic heterogeneity in lung and colorectal carcinoma as revealed by microsatellite analysis in plasma or tumor tissue DNA.
abstract: 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.
authors.affiliation: Laboratoire de Biochimie et de Biologie Moléculaire, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, Strasbourg, France. mariepierre.gaub@chru-strasbourg.fr
authors.forename: Michèle
authors.initials: M
authors.lastname: Beau-Faller
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Weber
authors.forename: Anne
authors.initials: A
authors.lastname: Schneider
authors.forename: Eric
authors.initials: E
authors.lastname: Guèrin
authors.forename: Bernard
authors.initials: B
authors.lastname: Gasser
authors.forename: Xavier
authors.initials: X
authors.lastname: Ducrocq
authors.forename: Daniel
authors.initials: D
authors.lastname: Jaeck
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Wihlm
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Quoix
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Gaub
mesh_terms: 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
chemical_list: D004273:DNA, Neoplasm