Abstract
BACKGROUND: Mucinous cystadenocarcinoma (MCA) of the breast is a rare and distinct type of mammary tract adenocarcinoma. Molecular alterations in breast MCA remain poorly characterized in current epidemiological data. METHODS: We summarized the clinicopathological characteristics and performed exome sequencing on formalin-fixed, paraffin-embedded blocks from three patients with mammary MCA culled from the surgical pathology archives of Chongqing University Cancer Hospital. The tumor mutation landscape of these patients was determined using whole-exome sequencing. We assessed cancer effect sizes and analyzed the contribution of mutational processes to each oncogenic variant, quantifying the extent to which each process contributed to tumorigenesis/cancer effects. RESULTS: Our analysis revealed that one of the three patient cohorts with advanced-stage breast MCA demonstrated aggressive clinical behavior, which contrasts with the typically reported indolent course of this rare malignancy. We also identified a significant mutant gene, bone morphogenetic protein 2 (BMP2), that is associated with breast MCA. Furthermore, we evaluated the expression by immunohistochemistry in patients with breast MCA and predicted the potential molecular functions of BMP2 in breast cancer through in silico analyses. CONCLUSION: This study provides new insights into the clinical and molecular features of breast MCA, suggesting that tumor stage is an important prognostic indicator. BMP2 emerged as a potential driver of tumor progression, and its utility as a predictive or prognostic biomarker warrants further investigation in larger cohorts. These findings may pave the way for improved prognostic assessment and novel therapeutic strategies targeting BMP2 in breast MCA.