Monoallelic expression characterizes a distinct molecular and clinical group of breast tumors

Monoallelic expression characterizes a distinct molecular and clinical group of breast tumors | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Monoallelic expression characterizes a distinct molecular and clinical group of breast tumors Mona Arabzadeh, Amartya Singh, Kyle Payne, Shridar Ganesan, Hossein Khiabanian This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8535132/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract In diploid cells, allelic imbalance occurs when gene alleles are expressed at different levels. To investigate the allelic imbalance landscape in tumor samples, we developed Interval-Based Allelic Imbalance Detection (IB-Aid), a quantitative framework that uses interval arithmetic to robustly distinguish monoallelic from biallelic gene expression by computing confidence intervals that account for sequencing measurement uncertainty. We applied this approach to The Cancer Genome Atlas Breast Invasive Carcinoma cohort and, through unsupervised gene enrichment analyses, identified a group of patients with a distinct monoallelic gene expression signature. These tumors were not previously classified into any established molecular subtype and exhibited mixed immunohistochemical (IHC) profiles. Notably, this group was enriched for Black/African American patients. Clinically, tumors in this subgroup were associated with poor overall survival, with outcomes comparable to the aggressive basal subtype. Together, these findings suggest a link between allelic imbalance and breast cancer development. Our results further implicate genetic and epigenetic mechanisms driving allelic imbalance as potential biomarkers for prognosis and the design of targeted treatment strategies. Health sciences/Biomarkers Biological sciences/Cancer Biological sciences/Computational biology and bioinformatics Biological sciences/Genetics Health sciences/Oncology Full Text Additional Declarations Competing interest reported. SG has been a consultant for KayoThera, Lunit, Ipsen, Roche, Merck, Foghorn Therapeutics, and EQRX, and has received research funding from Gandeeva and M2GEN. HK is a full-time employee of Regeneron Pharmaceuticals. All other authors declare no conflicts of interest. Supplementary Files SupplementaryNotes.pdf SupplementalTableS.zip Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 04 Mar, 2026 Reviewers agreed at journal 13 Feb, 2026 Reviewers agreed at journal 11 Feb, 2026 Reviewers invited by journal 11 Feb, 2026 Editor assigned by journal 12 Jan, 2026 Submission checks completed at journal 08 Jan, 2026 First submitted to journal 06 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8535132","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":590813687,"identity":"f59144d7-518c-4d7f-a78a-142bf46d0d7a","order_by":0,"name":"Mona Arabzadeh","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDklEQVRIiWNgGAWjYDADAyCWYGywQRI6QJyWNAYGNhK1HCasRbe99+AHhpp78ub8hx/e+LjjfL7B/faLjyv+MMjx3UjAqsXszLlkCYZjxYY7G44ZW848c9tywzGeYsOzbQzGkri03MgxkGBgS2DccLDBTJq37baBwTGeNMnGBobEDbi1GP9g+Jdgv+Ew+zfpv23nQFrSfzb8YajHo8VMgrEtIRHoHjNpxrYDQC3sxxgb2BgSDHD65YyZRWJfQvLOHp5iy962ZAPJYznMko1tEoYzzzzAruV4j/GND98SbLfzH99442ebnQHf4eMPPzb8sZHnO47dFjBAk+IBxxFu5VgAO3YHjYJRMApGwYgFAJmKZ2T+aqZ/AAAAAElFTkSuQmCC","orcid":"","institution":"Rutgers Cancer Institute of New Jersey","correspondingAuthor":true,"prefix":"","firstName":"Mona","middleName":"","lastName":"Arabzadeh","suffix":""},{"id":590813688,"identity":"edfccc73-426f-429d-a74a-eb354b44d8fb","order_by":1,"name":"Amartya Singh","email":"","orcid":"","institution":"Rutgers Cancer Institute of New Jersey","correspondingAuthor":false,"prefix":"","firstName":"Amartya","middleName":"","lastName":"Singh","suffix":""},{"id":590813689,"identity":"25aa03f6-1228-40e5-800a-91fb16e29e84","order_by":2,"name":"Kyle Payne","email":"","orcid":"","institution":"Rutgers Cancer Institute of New Jersey","correspondingAuthor":false,"prefix":"","firstName":"Kyle","middleName":"","lastName":"Payne","suffix":""},{"id":590813690,"identity":"14bfa835-3af9-4ff0-b0ff-3a7fc32f19ca","order_by":3,"name":"Shridar Ganesan","email":"","orcid":"","institution":"Rutgers Cancer Institute of New Jersey","correspondingAuthor":false,"prefix":"","firstName":"Shridar","middleName":"","lastName":"Ganesan","suffix":""},{"id":590813691,"identity":"e48e596e-97eb-44d2-b74c-52ac3732cf5b","order_by":4,"name":"Hossein Khiabanian","email":"","orcid":"","institution":"Rutgers Cancer Institute of New Jersey","correspondingAuthor":false,"prefix":"","firstName":"Hossein","middleName":"","lastName":"Khiabanian","suffix":""}],"badges":[],"createdAt":"2026-01-06 22:08:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8535132/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8535132/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":103051339,"identity":"58672f80-c929-4f0c-8ddb-8c52f80e6903","added_by":"auto","created_at":"2026-02-20 07:59:45","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":15030967,"visible":true,"origin":"","legend":"","description":"","filename":"ASEBRCA.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8535132/v1_covered_d7ae3276-cb74-4701-b061-d8451ccae60c.pdf"},{"id":103049467,"identity":"ae9333be-5a49-4bad-88ae-a10f8af98cc2","added_by":"auto","created_at":"2026-02-20 07:41:32","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":3494817,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryNotes.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8535132/v1/d7fc4ed49f5ea1d28c8c6ee6.pdf"},{"id":102814603,"identity":"97c721af-0cdd-4cd1-9410-52b6aea91c9a","added_by":"auto","created_at":"2026-02-17 05:22:27","extension":"zip","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":2862158,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalTableS.zip","url":"https://assets-eu.researchsquare.com/files/rs-8535132/v1/2017390778e4aaa66f6543bb.zip"}],"financialInterests":"Competing interest reported. 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To investigate the allelic imbalance landscape in tumor samples, we developed Interval-Based Allelic Imbalance Detection (IB-Aid), a quantitative framework that uses interval arithmetic to robustly distinguish monoallelic from biallelic gene expression by computing confidence intervals that account for sequencing measurement uncertainty. We applied this approach to The Cancer Genome Atlas Breast Invasive Carcinoma cohort and, through unsupervised gene enrichment analyses, identified a group of patients with a distinct monoallelic gene expression signature. These tumors were not previously classified into any established molecular subtype and exhibited mixed immunohistochemical (IHC) profiles. Notably, this group was enriched for Black/African American patients. Clinically, tumors in this subgroup were associated with poor overall survival, with outcomes comparable to the aggressive basal subtype. Together, these findings suggest a link between allelic imbalance and breast cancer development. Our results further implicate genetic and epigenetic mechanisms driving allelic imbalance as potential biomarkers for prognosis and the design of targeted treatment strategies.","manuscriptTitle":"Monoallelic expression characterizes a distinct molecular and clinical group of breast tumors","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-17 05:22:19","doi":"10.21203/rs.3.rs-8535132/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-03-04T09:26:02+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"3392598847053132550171166198778955546","date":"2026-02-13T06:44:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"106843236601615881414682602834895477267","date":"2026-02-11T08:37:30+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-11T05:56:24+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-13T01:24:14+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-09T04:17:50+00:00","index":"","fulltext":""},{"type":"submitted","content":"npj Breast Cancer","date":"2026-01-06T21:54:39+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"npj-breast-cancer","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"npjbcancer","sideBox":"Learn more about [npj Breast Cancer](http://www.nature.com/npjbcancer/)","snPcode":"41523","submissionUrl":"https://mts-npjbcancer.nature.com/","title":"npj Breast Cancer","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"NPJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ae377305-5f11-45a0-9b45-2b77e552d698","owner":[],"postedDate":"February 17th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":62872271,"name":"Health sciences/Biomarkers"},{"id":62872272,"name":"Biological sciences/Cancer"},{"id":62872273,"name":"Biological sciences/Computational biology and bioinformatics"},{"id":62872274,"name":"Biological sciences/Genetics"},{"id":62872275,"name":"Health sciences/Oncology"}],"tags":[],"updatedAt":"2026-02-17T05:22:19+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-17 05:22:19","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8535132","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8535132","identity":"rs-8535132","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}