title: Comparison of molecular changes in lung cancers in HIV-positive and HIV-indeterminate subjects.
abstract: BACKGROUND
  Human immunodeficiency virus (HIV) infection has been associated with an increasing incidence of malignancy, and HIV-infected persons have an increased incidence of primary lung carcinoma compared with the general population.
  
  
  OBJECTIVE
  To investigate the molecular changes present in HIV-associated lung tumors and compare them with those present in lung carcinomas arising in HIV-indeterminate subjects ("sporadic tumors").
  
  
  METHODS
  Convenience sample.
  
  
  METHODS
  Archival tissues from 11 HIV-positive persons and from 35 persons of indeterminate HIV status.
  
  
  METHODS
  University-based medical centers and affiliated hospitals.
  
  
  METHODS
  Analysis of frequency of loss of heterozygosity (LOH) and microsatellite alteration (MA) using polymerase chain reaction and 16 polymorphic microsatellite markers at 8 chromosomal regions frequently deleted in lung cancer. Presence of HIV and human papillomavirus (HPV) sequences.
  
  
  RESULTS
  The overall frequency of LOH at all chromosomal regions tested and the frequencies at most of the individual regions were similar in the 2 groups. Frequency of MA present in the HIV-associated tumors (0.18) was 6-fold higher than in sporadic tumors (0.03) (P<.001). At least 1 MA was present in 10 (91%) of 11 HIV-associated tumors vs 17 (48%) of 35 sporadic tumors (P=.02). Molecular changes were independent of tumor stage and gender. HIV and HPV sequences were not detected in the HIV-associated lung carcinomas.
  
  
  CONCLUSIONS
  Microsatellite alterations, which reflect widespread genomic instability, occur at greatly increased frequency in HIV-associated lung carcinomas. Although the mechanism underlying the development of increased MAs is unknown, it may play a crucial role in the development of many HIV-associated tumors.
authors.affiliation: Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas 75235-8593, USA.
authors.forename: I I
authors.initials: II
authors.lastname: Wistuba
authors.forename: C
authors.initials: C
authors.lastname: Behrens
authors.forename: S
authors.initials: S
authors.lastname: Milchgrub
authors.forename: A K
authors.initials: AK
authors.lastname: Virmani
authors.forename: J
authors.initials: J
authors.lastname: Jagirdar
authors.forename: B
authors.initials: B
authors.lastname: Thomas
authors.forename: H L
authors.initials: HL
authors.lastname: Ioachim
authors.forename: L A
authors.initials: LA
authors.lastname: Litzky
authors.forename: E M
authors.initials: EM
authors.lastname: Brambilla
authors.forename: J D
authors.initials: JD
authors.lastname: Minna
authors.forename: A F
authors.initials: AF
authors.lastname: Gazdar
mesh_terms: D000328:Adult; D004273:DNA, Neoplasm / Q000032:analysis*; D004279:DNA, Viral / Q000032:analysis; D006678:HIV / Q000235:genetics; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000150:complications* / Q000235:genetics / Q000473:pathology* / Q000821:virology; D018895:Microsatellite Repeats; D008875:Middle Aged; D027383:Papillomaviridae / Q000235:genetics; D016133:Polymerase Chain Reaction
chemical_list: D004273:DNA, Neoplasm; D004279:DNA, Viral