Dataset Information

Genomic profiling of multiple breast cancer reveals inter-lesional heterogeneity.

ABSTRACT:

Background

Multiplicity in breast cancer is common. Studies on multiple breast cancers have revealed high concordance in biomarker status among individual lesions. However, genomic differences among multiple lesions are not well-established. We aimed to investigate the potential genomic heterogeneity of multiple breast cancer.

Methods

Twenty-one patients with radiologically and histologically evident multiple breast cancer with similar histology were included. Two lesions from each of the 21 patients were selected, and biomarker status was evaluated for each lesion. Capture-based targeted next-generation sequencing was performed using a cancer gene panel consisting of 170 genes.

Results

We identified discordance in intrinsic subtype in 2 (10%) of the 21 patients. Pathogenic mutations were detected in 13 of the 21 patients, of whom 11 shared oncogenic variants in the two lesions. The remaining two patients yielded different mutation results for TP53, ATM, and PIK3CA. Difference in copy number alteration was observed in 7 (33%) of the 21 patients including ERBB2 (n = 2), FGFR1 (n = 2), and FGFR2 (n = 1) genes.

Conclusion

Despite similar histologic features of the individual lesions, inter-lesional genomic difference was identified in more than one-third of the patients. Inter-lesional genomic heterogeneity needs to be considered when performing a genomic test in multiple breast cancers.

SUBMITTER: Ahn S

PROVIDER: S-EPMC7054255 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Publications

Genomic profiling of multiple breast cancer reveals inter-lesional heterogeneity.

Ahn Soomin S Kim Hyun Jeong HJ Kang Eunyoung E Kim Eun-Kyu EK Kim Se Hyun SH Kim Jee Hyun JH Kim In Ah IA Park So Yeon SY

British journal of cancer 20200113 5

<h4>Background</h4>Multiplicity in breast cancer is common. Studies on multiple breast cancers have revealed high concordance in biomarker status among individual lesions. However, genomic differences among multiple lesions are not well-established. We aimed to investigate the potential genomic heterogeneity of multiple breast cancer.<h4>Methods</h4>Twenty-one patients with radiologically and histologically evident multiple breast cancer with similar histology were included. Two lesions from eac ...[more]

PMID: 31929516

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Project description:BackgroundHeterogeneity of immune gene expression patterns of luminal breast cancer (BC), which is clinically heterogeneous and overall considered as low immunogenic, has not been well studied especially in non-European populations. Here, we aimed at characterizing the immune gene expression profile of luminal BC in an Asian population and associating it with patient characteristics and tumor genomic features.MethodsWe performed immune gene expression profiling of tumor and adjacent normal tissue in 92 luminal BC patients from Hong Kong using RNA-sequencing data and used unsupervised consensus clustering to stratify tumors. We then used luminal patients from The Cancer Genome Atlas (TCGA, N = 564) and a Korean breast cancer study (KBC, N = 112) as replication datasets.ResultsBased on the expression of 130 immune-related genes, luminal tumors were stratified into three distinct immune subtypes. Tumors in one subtype showed higher level of tumor-infiltrating lymphocytes (TILs), characterized by T cell gene activation, higher expression of immune checkpoint genes, higher nonsynonymous mutation burden, and higher APOBEC-signature mutations, compared with other luminal tumors. The high-TIL subtype was also associated with lower ESR1/ESR2 expression ratio and increasing body mass index. The comparison of the immune profile in tumor and matched normal tissue suggested a tumor-derived activation of specific immune responses, which was only seen in high-TIL patients. Tumors in a second subtype were characterized by increased expression of interferon-stimulated genes and enrichment for TP53 somatic mutations. The presence of three immune subtypes within luminal BC was replicated in TCGA and KBC, although the pattern was more similar in Asian populations. The germline APOBEC3B deletion polymorphism, which is prevalent in East Asian populations and was previously linked to immune activation, was not associated with immune subtypes in our study. This result does not support the hypothesis that the germline APOBEC3B deletion polymorphism is the driving force for immune activation in breast tumors in Asian populations.ConclusionOur findings suggest that immune gene expression and associated genomic features could be useful to further stratify luminal BC beyond the current luminal A/B classification and a subset of luminal BC patients may benefit from checkpoint immunotherapy, at least in Asian populations.

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Dataset Information

Genomic profiling of multiple breast cancer reveals inter-lesional heterogeneity.

Background

Methods

Results

Conclusion

Publications

Genomic profiling of multiple breast cancer reveals inter-lesional heterogeneity.

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