Comparison of molecular changes in lung cancers in HIV-positive and HIV- indeterminate subjects

Ignacio I. Wistuba, Carmen Behrens, Sara Milchgrub, Arvind K. Virmani, Jaishree Jagirdar, Bilue Thomas, Harry L. Ioachim, Leslie A. Litzky, Elisabeth M. Brambilla, John D. Minna, Adi F. Gazdar

Research output: Contribution to journalArticle

115 Scopus citations

Abstract

Context. - 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'). Design. - Convenience sample. Subjects. - Archival tissues from 11 HIV- positive persons and from 35 persons of indeterminate HIV status. Setting. - University-based medical centers and affiliated hospitals. Main Outcome Measures. - 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.

Original languageEnglish (US)
Pages (from-to)1554-1559
Number of pages6
JournalJournal of the American Medical Association
Volume279
Issue number19
DOIs
StatePublished - May 20 1998

    Fingerprint

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Wistuba, I. I., Behrens, C., Milchgrub, S., Virmani, A. K., Jagirdar, J., Thomas, B., Ioachim, H. L., Litzky, L. A., Brambilla, E. M., Minna, J. D., & Gazdar, A. F. (1998). Comparison of molecular changes in lung cancers in HIV-positive and HIV- indeterminate subjects. Journal of the American Medical Association, 279(19), 1554-1559. https://doi.org/10.1001/jama.279.19.1554