{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T09:38:16Z","timestamp":1793093896008,"version":"4.5.0"},"reference-count":40,"publisher":"SAGE Publications","issue":"11","license":[{"start":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T00:00:00Z","timestamp":1772928000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Dent Res"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:p>\n                    Adenoid cystic carcinoma (ACC) is a rare malignancy with 3 components (tubular, cribriform, and solid), and these components often coexist in the same patient. In the past few decades, great strides have been made in the pathological classification of ACC. However, due to the complexity of the pathological morphology, establishing a unified grading\/assessment standard for clinical implementation process remains challenging. This study aimed to develop improved prognostic biomarkers to assist clinical pathological assessment at the molecular level. We used laser capture microdissection to isolate tumor microsamples with specific pathological features (solid, cribriform, and tubular component) and paracancerous normal glands from 100 patients, then performed DNA sequencing (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 955) and RNA sequencing (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 723) to obtain the genome and transcriptome profile, including copy number variation (CNV) type, gene fusion, and transcriptional expression. We found that CNV and gene fusion patterns differed among the 3 pathological subtypes and correlated with clinical outcome. We also found a mutually exclusive relationship between MYBL1::NFIB fusion and 6q-loss, and they displayed distinct different transcriptional profiles. We discovered that molecular markers 6q-loss and 14q-loss were strongly associated with poor prognosis in ACC. Patients with 6q-loss or 14q-loss had a higher risk of tumor metastasis and recurrence, whereas MYB::NFIB and MYBL1::NFIB fusions showed no adverse prognostic impact. Based on these findings, we propose a new CNV-based molecular classification that stratifies patients into the subgroups of 6q-loss, 14q-loss, and others. The molecular classification method increased the prognostic accuracy from 74.49% (the pathological method) to now 82.65%, especially in cribriform patients (increased from 64% to 80%). Fluorescence in situ hybridization\u2013based detection of 6q-loss and 14q-loss by probe ESR1-6q25 and FOS-14q24 provided a rapid and clinically feasible validation in ACC prognostic assessment. Further multicohort and multifactor analysis demonstrated the robustness and independence of the prognostic value in overall survival and metastasis-free survival of the molecular classification method.\n                  <\/jats:p>","DOI":"10.1177\/00220345261416398","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T10:28:42Z","timestamp":1773224922000},"page":"1451-1461","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Genomic and Transcriptomic Analysis of Salivary Adenoid Cystic Carcinomas Defines Molecular Subtypes"],"prefix":"10.1177","volume":"105","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9393-9008","authenticated-orcid":false,"given":"L.","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Oral Pathology, Peking University School and Hospital of Stomatology &amp; National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; National Engineering Research Center of Oral Biomaterials and Digital Medical Devices &amp; Beijing Key Laboratory of Digital Stomatology &amp; NHC Key Laboratory of Digital Stomatology &amp; NMPA Key Laboratory for Dental Materials, Haidian District, Beijing, Mainland China"},{"name":"Research Unit of Precision Pathologic Diagnosis in Tumors of the Oral and Maxillofacial Regions, Chinese Academy of Medical Sciences (2019RU034), Beijing, Mainland China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9228-7712","authenticated-orcid":false,"given":"Y.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, Mainland China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5978-7189","authenticated-orcid":false,"given":"M.","family":"Hao","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Tsinghua University, Beijing, Mainland China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9092-2605","authenticated-orcid":false,"given":"Y.","family":"Lou","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, Peking University School and Hospital of Stomatology &amp; National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; National Engineering Research Center of Oral Biomaterials and Digital Medical Devices &amp; Beijing Key Laboratory of Digital Stomatology &amp; NHC Key Laboratory of Digital Stomatology &amp; NMPA Key Laboratory for Dental Materials, Haidian District, Beijing, Mainland China"},{"name":"Research Unit of Precision Pathologic Diagnosis in Tumors of the Oral and Maxillofacial Regions, Chinese Academy of Medical Sciences (2019RU034), Beijing, Mainland China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6440-2434","authenticated-orcid":false,"given":"L.","family":"Liu","sequence":"additional","affiliation":[{"name":"Changping Laboratory, Changping District, Beijing, Mainland China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7480-6400","authenticated-orcid":false,"given":"Z.","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, Peking University School and Hospital of Stomatology &amp; National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; National Engineering Research Center of Oral Biomaterials and Digital Medical Devices &amp; Beijing Key Laboratory of Digital Stomatology &amp; NHC Key Laboratory of Digital Stomatology &amp; NMPA Key Laboratory for Dental Materials, Haidian District, Beijing, Mainland China"},{"name":"Research Unit of Precision Pathologic Diagnosis in Tumors of the Oral and Maxillofacial Regions, Chinese Academy of Medical Sciences (2019RU034), Beijing, Mainland China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2998-1451","authenticated-orcid":false,"given":"Y.","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, Peking University School and Hospital of Stomatology &amp; National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; National Engineering Research Center of Oral Biomaterials and Digital Medical Devices &amp; Beijing Key Laboratory of Digital Stomatology &amp; NHC Key Laboratory of Digital Stomatology &amp; NMPA Key Laboratory for Dental Materials, Haidian District, Beijing, Mainland China"},{"name":"Research Unit of Precision Pathologic Diagnosis in Tumors of the Oral and Maxillofacial Regions, Chinese Academy of Medical Sciences (2019RU034), Beijing, Mainland China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, Peking University School and Hospital of Stomatology &amp; National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; National Engineering Research Center of Oral Biomaterials and Digital Medical Devices &amp; Beijing Key Laboratory of Digital Stomatology &amp; NHC Key Laboratory of Digital Stomatology &amp; NMPA Key Laboratory for Dental Materials, Haidian District, Beijing, Mainland China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9659-0698","authenticated-orcid":false,"given":"J.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, Peking University School and Hospital of Stomatology &amp; National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; National Engineering Research Center of Oral Biomaterials and Digital Medical Devices &amp; Beijing Key Laboratory of Digital Stomatology &amp; NHC Key Laboratory of Digital Stomatology &amp; NMPA Key Laboratory for Dental Materials, Haidian District, Beijing, Mainland China"},{"name":"Research Unit of Precision Pathologic Diagnosis in Tumors of the Oral and Maxillofacial Regions, Chinese Academy of Medical Sciences (2019RU034), Beijing, Mainland China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6725-7925","authenticated-orcid":false,"given":"J.","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Tsinghua University, Beijing, Mainland China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2288-7947","authenticated-orcid":false,"given":"C.-X.","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, Peking University School and Hospital of Stomatology &amp; National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; National Engineering Research Center of Oral Biomaterials and Digital Medical Devices &amp; Beijing Key Laboratory of Digital Stomatology &amp; NHC Key Laboratory of Digital Stomatology &amp; NMPA Key Laboratory for Dental Materials, Haidian District, Beijing, Mainland China"},{"name":"Research Unit of Precision Pathologic Diagnosis in Tumors of the Oral and Maxillofacial Regions, Chinese Academy of Medical Sciences (2019RU034), Beijing, Mainland China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5983-2985","authenticated-orcid":false,"given":"T.","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, Peking University School and Hospital of Stomatology &amp; National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; National Engineering Research Center of Oral Biomaterials and Digital Medical Devices &amp; Beijing Key Laboratory of Digital Stomatology &amp; NHC Key Laboratory of Digital Stomatology &amp; NMPA Key Laboratory for Dental Materials, Haidian District, Beijing, Mainland China"},{"name":"Research Unit of Precision Pathologic Diagnosis in Tumors of the Oral and Maxillofacial Regions, Chinese Academy of Medical Sciences (2019RU034), Beijing, Mainland China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,3,8]]},"reference":[{"key":"e_1_3_2_2_1","doi-asserted-by":"crossref","unstructured":"Akbaba S et al. 2020. Large German multicenter experience on the treatment outcome of 207 patients with adenoid cystic carcinoma of the major salivary glands. Front Oncol. 10:593379. https:\/\/doi.org\/10.3389\/fonc.2020.593379","DOI":"10.3389\/fonc.2020.593379"},{"key":"e_1_3_2_3_1","doi-asserted-by":"crossref","unstructured":"Beaudry VG et al. 2010. Loss of the p53\/p63 regulated desmosomal protein Perp promotes tumorigenesis. PLoS Genet. 6(10):e1001168. https:\/\/doi.org\/10.1371\/journal.pgen.1001168","DOI":"10.1371\/journal.pgen.1001168"},{"key":"e_1_3_2_4_1","doi-asserted-by":"crossref","unstructured":"Bhayani MK et al. 2012. Prognosis and risk factors for early-stage adenoid cystic carcinoma of the major salivary glands. Cancer. 118(11):2872\u20132878. https:\/\/doi.org\/10.1002\/cncr.26549","DOI":"10.1002\/cncr.26549"},{"key":"e_1_3_2_5_1","doi-asserted-by":"crossref","unstructured":"Brayer KJ Frerich CA Kang H Ness SA. 2016. Recurrent fusions in MYB and MYBLl1 define a common transcription factor-driven oncogenic pathway in salivary gland adenoid cystic carcinoma. Cancer Discov. 6(2):176\u2013187. https:\/\/doi.org\/10.1158\/2159-8290.cd-15-0859","DOI":"10.1158\/2159-8290.CD-15-0859"},{"key":"e_1_3_2_6_1","doi-asserted-by":"crossref","unstructured":"Chen X et al. 2023. A membrane-associated MHC-I inhibitory axis for cancer immune evasion. Cell. 186(18):3903\u20133920.e21. https:\/\/doi.org\/10.1016\/j.cell.2023.07.016","DOI":"10.1016\/j.cell.2023.07.016"},{"key":"e_1_3_2_7_1","doi-asserted-by":"crossref","unstructured":"Cordesmeyer R et al. 2020. Shallow whole genome sequencing of adenoid cystic carcinomas of the salivary glands identifies specific chromosomal aberrations related to tumor progression. 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Activating NOTCH1 mutations define a distinct subgroup of patients with adenoid cystic carcinoma who have poor prognosis propensity to bone and liver metastasis and potential responsiveness to NOTCH1 inhibitors. J Clin Oncol. 35(3):352\u2013360. https:\/\/doi.org\/10.1200\/jco.2016.67.5264","DOI":"10.1200\/JCO.2016.67.5264"},{"key":"e_1_3_2_11_1","doi-asserted-by":"crossref","unstructured":"Ferrarotto R et al. 2021. Proteogenomic analysis of salivary adenoid cystic carcinomas defines molecular subtypes and identifies therapeutic targets. Clin Cancer Res. 27(3):852\u2013864. https:\/\/doi.org\/10.1158\/1078-0432.ccr-20-1192","DOI":"10.1158\/1078-0432.CCR-20-1192"},{"key":"e_1_3_2_12_1","doi-asserted-by":"crossref","unstructured":"Frerich CA et al. 2017. Transcriptomes define distinct subgroups of salivary gland adenoid cystic carcinoma with different driver mutations and outcomes. 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Rearrangements expression and clinical significance of MYB and MYBL1 in adenoid cystic carcinoma: a multi-institutional study. Cancers (Basel). 14(15):3691. https:\/\/doi.org\/10.3390\/cancers14153691","DOI":"10.3390\/cancers14153691"},{"key":"e_1_3_2_27_1","doi-asserted-by":"crossref","unstructured":"Perzin KH Gullane P Clairmont AC. 1978. Adenoid cystic carcinomas arising in salivary glands: a correlation of histologic features and clinical course. Cancer. 42(1):265\u2013282. https:\/\/doi.org\/10.1002\/1097-0142(197807)42:1%3C265::aid-cncr2820420141%3E3.0.co;2-z","DOI":"10.1002\/1097-0142(197807)42:1<265::AID-CNCR2820420141>3.0.CO;2-Z"},{"key":"e_1_3_2_28_1","doi-asserted-by":"crossref","unstructured":"Rao PH et al. 2008. Deletion of 1p32-p36 is the most frequent genetic change and poor prognostic marker in adenoid cystic carcinoma of the salivary glands. 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Chromosome 6 deletion and candidate tumor suppressor genes in adenoid cystic carcinoma. Cancer Lett. 236(2):309\u2013317. https:\/\/doi.org\/10.1016\/j.canlet.2005.05.049","DOI":"10.1016\/j.canlet.2005.05.049"},{"key":"e_1_3_2_32_1","doi-asserted-by":"crossref","unstructured":"Spiro RH Huvos AG Strong EW. 1974. Adenoid cystic carcinoma of salivary origin. A clinicopathologic study of 242 cases. Am J Surg. 128(4):512\u2013520. https:\/\/doi.org\/10.1016\/0002-9610(74)90265-7","DOI":"10.1016\/0002-9610(74)90265-7"},{"key":"e_1_3_2_33_1","doi-asserted-by":"crossref","unstructured":"Stallmach I et al. 2002. Loss of heterozygosity at chromosome 6q23\u201325 correlates with clinical and histologic parameters in salivary gland adenoid cystic carcinoma. Virchows Archiv. 440(1):77\u201384. https:\/\/doi.org\/10.1007\/s004280100523","DOI":"10.1007\/s004280100523"},{"key":"e_1_3_2_34_1","doi-asserted-by":"crossref","unstructured":"Szanto PA Luna MA Tortoledo ME White RA. 1984. Histologic grading of adenoid cystic carcinoma of the salivary glands. Cancer. 54(6):1062\u20131069. https:\/\/doi.org\/10.1002\/1097-0142(19840915)54:6%3C1062::aid-cncr2820540622%3E3.0.co;2-e","DOI":"10.1002\/1097-0142(19840915)54:6<1062::AID-CNCR2820540622>3.0.CO;2-E"},{"key":"e_1_3_2_35_1","doi-asserted-by":"crossref","unstructured":"Togashi Y et al. 2018. MYB and MYBL1 in adenoid cystic carcinoma: diversity in the mode of genomic rearrangement and transcripts. Modern Pathol. 31(6):934\u2013946. https:\/\/doi.org\/10.1038\/s41379-018-0008-8","DOI":"10.1038\/s41379-018-0008-8"},{"key":"e_1_3_2_36_1","doi-asserted-by":"crossref","unstructured":"Van Weert S van der Waal I Witte BI Leemans CR Bloemena E. 2015. Histopathological grading of adenoid cystic carcinoma of the head and neck: analysis of currently used grading systems and proposal for a simplified grading scheme. 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