{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:59:14Z","timestamp":1790521154638,"version":"4.1.0"},"reference-count":24,"publisher":"American Society of Hematology","issue":"11","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,3,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Follicular lymphoma B cells undergo continuous somatic hypermutation (SHM) of their immunoglobulin variable region genes, generating a heterogeneous tumor population. SHM introduces DNA sequences encoding N-glycosylation sites asparagine-X-serine\/threonine (N-gly sites) within the V-region that are rarely found in normal B-cell counterparts. Unique attached oligomannoses activate B-cell receptor signaling pathways after engagement with calcium-dependent lectins expressed by tissue macrophages. This novel interaction appears critical for tumor growth and survival. To elucidate the significance of N-gly site presence and loss during ongoing SHM, we tracked site behavior during tumor evolution and progression in a diverse group of patients through next-generation sequencing. A hierarchy of subclones was visualized through lineage trees based on SHM semblance between subclones and their discordance from the germline sequence. We observed conservation of N-gly sites in more than 96% of subclone populations within and across diagnostic, progression, and transformation events. Rare N-gly-negative subclones were lost or negligible from successive events, in contrast to N-gly-positive subclones, which could additionally migrate between anatomical sites. Ongoing SHM of the N-gly sites resulted in subclones with different amino acid compositions across disease events, yet the vast majority of resulting DNA sequences still encoded for an N-gly site. The selection and expansion of only N-gly-positive subclones is evidence of the tumor cells\u2019 dependence on sites, despite the changing genomic complexity as the disease progresses. N-gly sites were gained in the earliest identified lymphoma cells, indicating they are an early and stable event of pathogenesis. Targeting the inferred mannose-lectin interaction holds therapeutic promise.<\/jats:p>","DOI":"10.1182\/blood.2019002279","type":"journal-article","created":{"date-parts":[[2020,1,14]],"date-time":"2020-01-14T03:49:26Z","timestamp":1578973766000},"page":"834-844","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":41,"title":["IGHV sequencing reveals acquired N-glycosylation sites as a clonal and stable event during follicular lymphoma evolution"],"prefix":"10.1182","volume":"135","author":[{"given":"Mariette","family":"Odabashian","sequence":"first","affiliation":[{"name":"Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Carlotti","sequence":"first","affiliation":[{"name":"Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom; 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Cancer Institute, Queen Mary University of London, London, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2211-1831","authenticated-orcid":false,"given":"Francesco","family":"Forconi","sequence":"first","affiliation":[{"name":"Cancer Sciences Division, Somers Cancer Sciences Building, University of Southampton, Southampton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Freda K.","family":"Stevenson","sequence":"first","affiliation":[{"name":"Cancer Sciences Division, Somers Cancer Sciences Building, University of Southampton, Southampton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariarita","family":"Calaminici","sequence":"first","affiliation":[{"name":"Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom; 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