{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:41:30Z","timestamp":1785426090498,"version":"3.56.0"},"posted":{"date-parts":[[2025,8,25]]},"group-title":"Cancer Biology","reference-count":21,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:00:00Z","timestamp":1756080000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["R01CA252378"],"award-info":[{"award-number":["R01CA252378"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["S10OD028483"],"award-info":[{"award-number":["S10OD028483"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"name":"The Shear Family Foundation"},{"id":[{"id":"https:\/\/ror.org\/0348ff195","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,8,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Breast cancer is a heterogeneous disease with numerous histological subtypes. Invasive lobular cancer (ILC) is the most common special subtype, accounting for 10-15% of all breast cancers. The pathognomonic feature of ILC is the loss of E-cadherin (CDH1), which leads to a unique single-file growth pattern of discohesive cells. Although ILCs show better prognostic factors than the most common No Special Type (NST) of breast cancer, patients with ILC have worse long-term outcomes, which is not well understood. In this study, we aimed to identify and characterize Patient-Derived Xenograft (PDX) models of ILC based upon the presence of truncating\n                  <jats:italic>CDH1<\/jats:italic>\n                  mutations and\/or low\n                  <jats:italic>CDH1<\/jats:italic>\n                  mRNA expression among 128 human breast cancer PDX models. We selected 8 PDX models for validation using Immunohistochemical (IHC) analysis for E-Cadherin, p120, ER, PR, and HER2. We confirmed that seven of these PDX models are indeed ILC while one was identified as mixed NST-ILC PDX. Molecular analysis of the confirmed ILC PDX models showed enrichment of truncating\n                  <jats:italic>CDH1<\/jats:italic>\n                  mutations, significantly lower levels of\n                  <jats:italic>CDH1<\/jats:italic>\n                  mRNA expression and predominantly luminal subtypes compared to NST PDX models, in line with the molecular characteristics of human ILC disease. The commonly altered genes in the ILC PDX models included\n                  <jats:italic>PIK3CA<\/jats:italic>\n                  (57%),\n                  <jats:italic>CDH1<\/jats:italic>\n                  (57%) and\n                  <jats:italic>TP53<\/jats:italic>\n                  (57%) among others. Our study confirms and characterizes new ILC PDX models, offering valuable tools to advance our understanding of human ILC biology and support the development of innovative treatment strategies.\n                <\/jats:p>","DOI":"10.1101\/2025.08.21.669685","type":"posted-content","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T05:05:12Z","timestamp":1756184712000},"source":"Crossref","is-referenced-by-count":0,"title":["Identification and Credentialing of Patient Derived Xenograft Models of Invasive Lobular Breast Carcinoma using Multi-omics and Histopathology assessment"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5001-6092","authenticated-orcid":false,"given":"Jagmohan","family":"Hooda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer M","family":"Atkinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osama Shiraz","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Yates","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel D","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgan","family":"DeBerry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Cairo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Schiavini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiu-Wen","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Zipeto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohit","family":"Bhargava","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffi","family":"Oesterreich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9917-514X","authenticated-orcid":false,"given":"Adrian V","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025082816450809000_2025.08.21.669685v1.1","unstructured":"Society, A.C. , Cancer Facts & Figures, in American Cancer Society. 2025."},{"key":"2025082816450809000_2025.08.21.669685v1.2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21871"},{"key":"2025082816450809000_2025.08.21.669685v1.3","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1995.tb00301.x"},{"key":"2025082816450809000_2025.08.21.669685v1.4","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.22716"},{"key":"2025082816450809000_2025.08.21.669685v1.5","first-page":"494","article-title":"Invasive lobular carcinoma of the breast: clinicopathological features and patient outcomes","volume":"92","year":"2021","journal-title":"Ann Ital Chir"},{"issue":"11","key":"2025082816450809000_2025.08.21.669685v1.6","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1093\/jnci\/djac157","article-title":"Clinicopathological Features and Outcomes Comparing Patients With Invasive Ductal and Lobular Breast Cancer","volume":"114","year":"2022","journal-title":"J Natl Cancer Inst"},{"key":"2025082816450809000_2025.08.21.669685v1.7","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-022-06572-w"},{"issue":"2","key":"2025082816450809000_2025.08.21.669685v1.8","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1038\/s43018-022-00337-6","article-title":"A human breast cancer-derived xenograft and organoid platform for drug discovery and precision oncology","volume":"3","year":"2022","journal-title":"Nat Cancer"},{"key":"2025082816450809000_2025.08.21.669685v1.9","doi-asserted-by":"crossref","unstructured":"Tandon, V. , et al., Dual inhibition of HSF1 and DYRK2 impedes cancer progression. 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