Multiplatform Genomic and Transcriptomic Profiling of Breast Carcinomas with an Invasive Micropapillary Component.
- 1Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea.
- 2Department of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, Republic of Korea.
- 3Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul 06351, Republic of Korea.
Abstract
Background/Objectives: Invasive micropapillary carcinoma (IMPC) of the breast is a rare subtype with a strong propensity for lymph node metastasis, but its molecular features remain incompletely defined. We characterized the genomic and transcriptomic features of breast carcinomas with an invasive micropapillary component. Methods: Thirteen tumors with a micropapillary component of at least 10%, including four pure IMPCs, were analyzed by targeted sequencing (n = 11), whole-exome sequencing with array comparative genomic hybridization (n = 2), and whole-transcriptome sequencing (n = 9). Alteration frequencies were compared with TCGA-BRCA across all 375 panel genes, with multiple-testing correction and a sensitivity analysis restricted to truncating and hotspot variants. Results:TP53 was the most frequently altered gene (72.7%), followed by ERBB2 amplification (45.5%); PIK3CA and GATA3 were each altered in 27.3%. Four rarely mutated genes were more frequent than in TCGA-BRCA after correction, but these differences were based on few tumors and predominantly on uncertain missense variants and were not retained under the stringent definition. Recurrent high-level amplification was concentrated in 17q12-q21, and both pure IMPCs analyzed by array comparative genomic hybridization showed 8q gain. All five tumors with panel ERBB2 amplification were HER2-positive by immunohistochemistry, and TCGA-anchored PAM50 classified all three HER2-positive transcriptomes as HER2-enriched. Fourteen fusion transcripts were detected, none recurrent. Conclusions: These findings support a heterogeneous molecular landscape characterized by established breast cancer drivers, recurrent copy-number changes involving 8q and 17q, predominantly private fusion events, and cross-platform concordance of ERBB2 amplification with HER2 protein expression and PAM50 HER2-enriched classification.
Related
- Comparative clinical and molecular profiling of papillary thyroid carcinomas with unilateral and bilateral lateral lymph node metastasis: a retrospective cohort study.
- Integrative genomic profiling of large-cell neuroendocrine carcinomas reveals distinct subtypes of high-grade neuroendocrine lung tumors
- An interpretable whole-blood transcriptomic model for Parkinson disease identification and molecular profiling
- GeoMx Digital Spatial Profiler Enables Layer-Specific Spatial Transcriptomic Profiling of the Human Retina: A Proof-of-Concept Study from Post-Coronovirus Disease 2019 Donor Tissue
- Transcriptomic Profiling Reveals METTL26 as a Potential Biomarker in Head and Neck Squamous Cell Carcinoma with Independent Validation in Oral Squamous Cell Carcinoma
BibTeX
@article{lee2026multiplatform,
title = {{Multiplatform Genomic and Transcriptomic Profiling of Breast Carcinomas with an Invasive Micropapillary Component.}},
author = {Boram Lee and Je-Gun Joung and Woong-Yang Park and Hyunwoo Lee and Eun Yoon Cho},
journal = {Genes},
year = {2026},
month = sep,
doi = {10.3390/genes17101190},
url = {https://europepmc.org/article/MED/42938306},
note = {CC BY},
}
RIS
TY - JOUR
TI - Multiplatform Genomic and Transcriptomic Profiling of Breast Carcinomas with an Invasive Micropapillary Component.
AU - Boram Lee
AU - Je-Gun Joung
AU - Woong-Yang Park
AU - Hyunwoo Lee
AU - Eun Yoon Cho
PY - 2026
DA - 2026/09/25
JO - Genes
DO - 10.3390/genes17101190
UR - https://europepmc.org/article/MED/42938306
AB - Background/Objectives: Invasive micropapillary carcinoma (IMPC) of the breast is a rare subtype with a strong propensity for lymph node metastasis, but its molecular features remain incompletely defined. We characterized the genomic and transcriptomic features of breast carcinomas with an invasive micropapillary component. Methods: Thirteen tumors with a micropapillary component of at least 10%, including four pure IMPCs, were analyzed by targeted sequencing (n = 11), whole-exome sequencing with array comparative genomic hybridization (n = 2), and whole-transcriptome sequencing (n = 9). Alteration frequencies were compared with TCGA-BRCA across all 375 panel genes, with multiple-testing correction and a sensitivity analysis restricted to truncating and hotspot variants. Results:TP53 was the most frequently altered gene (72.7%), followed by ERBB2 amplification (45.5%); PIK3CA and GATA3 were each altered in 27.3%. Four rarely mutated genes were more frequent than in TCGA-BRCA after correction, but these differences were based on few tumors and predominantly on uncertain missense variants and were not retained under the stringent definition. Recurrent high-level amplification was concentrated in 17q12-q21, and both pure IMPCs analyzed by array comparative genomic hybridization showed 8q gain. All five tumors with panel ERBB2 amplification were HER2-positive by immunohistochemistry, and TCGA-anchored PAM50 classified all three HER2-positive transcriptomes as HER2-enriched. Fourteen fusion transcripts were detected, none recurrent. Conclusions: These findings support a heterogeneous molecular landscape characterized by established breast cancer drivers, recurrent copy-number changes involving 8q and 17q, predominantly private fusion events, and cross-platform concordance of ERBB2 amplification with HER2 protein expression and PAM50 HER2-enriched classification.
SN - 2073-4425
ER -