학술논문
Comparison of molecular changes in lung cancers in HIV-positive and HIV-indeterminate subjects
Document Type
Academic Journal
Author
Source
JAMA, The Journal of the American Medical Association. May 20, 1998, Vol. v279 Issue n19, p1554, 5 p.
Subject
Language
ISSN
0098-7484
Abstract
Alterations in microsatellite DNA appear to be common in HIV patients who have lung cancer. Microsatellite DNA are short sequences DNA that are highly repetitious. Researchers used DNA analysis to identify molecular changes in several chromosome locations that are often deleted in lung cancer in 11 HIV-positive people with lung cancer and 35 HIV-negative people with lung cancer. The frequency of microsatellite DNA alterations was 6 times higher in the HIV patients compared to the HIV-negative patients. Over 90% of the HIV patients had a microsatellite DNA alteration, compared to 48% of the HIV-negative patients.
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 [is less than] .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. JAMA. 1998;279:1554-1559
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 [is less than] .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. JAMA. 1998;279:1554-1559