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While a single case cannot establish causality, we describe here an investigation of a 74-year-old male PWH with de novo high-grade neuroendocrine small cell lung carcinoma. To investigate the potential contribution of HIV to cancer development, we performed HIV integration site sequencing on blood, tumor, and non-tumor tissue samples from the patient. We analyzed integration site distribution, clonal expansion, and associated gene disruption. Phosphatase and Tensin Homolog (PTEN) expression was evaluated using immunofluorescence and microscopy. A total of 174 unique HIV integration sites were identified, with 29.9% (52\/174) located in clonally expanded cells. The most frequent integration site in clonally expanded cells was within the PTEN gene, representing 4.2% to 16.7% of all HIV-infected cells across samples. PTEN expression was markedly reduced in tumor regions relative to non-tumor tissue. Areas positive for HIV p24 antigen showed minimal PTEN expression. These findings suggest that HIV integration into the PTEN gene, coupled with clonal expansion of HIV-infected cells, may impair anti-tumor immune responses and promote cancer progression in PWH.<\/jats:p>","DOI":"10.3390\/curroncol32070389","type":"journal-article","created":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T11:20:11Z","timestamp":1751628011000},"page":"389","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["HIV Integration into the PTEN Gene and Its Tumor Microenvironment Implications for Lung Cancer"],"prefix":"10.3390","volume":"32","author":[{"given":"Davey M.","family":"Smith","sequence":"first","affiliation":[{"name":"Department of Medicine, University of California, San Diego, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5845-9146","authenticated-orcid":false,"given":"Elizabeth F.","family":"Rowland","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL 61820, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Gianella","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Diego, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandip Pravin","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Diego, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Solso","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Diego, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl","family":"Dullano","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Diego, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Deiss","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Diego, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria","family":"Wells","sequence":"additional","affiliation":[{"name":"Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Ignacio","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Diego, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma","family":"Caballero","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Diego, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magali","family":"Porrachia","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Diego, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9051-3819","authenticated-orcid":false,"given":"Collin","family":"Kieffer","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL 61820, USA"},{"name":"Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61820, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9490-3857","authenticated-orcid":false,"given":"Antoine","family":"Chaillon","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Diego, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"(2017). 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