Two progressed malignant phyllodes tumors of the breast harbor alterations in genes frequently involved in other advanced cancers

• Published in: Orphanet journal of rare diseases Vol. 16; no. 1; pp. 1 - 363
• Main Authors: Reinisch, Mattea, Kuemmel, Sherko, Breit, Elisabeth, Theuerkauf, Ingo, Harrach, Hakima, Schindowski, Dorothea, Moka, Detlef, Bettstetter, Marcus, Bruzas, Simona, Chiari, Ouafaa
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 16-08-2021; BioMed Central; BMC
• Subjects: Adenomatous polyposis coli; Advanced cancer; Breast; Breast cancer; Breast tumors; Cancer therapies; Case studies; Chemotherapy; Development and progression; Diagnosis; Epidermal growth factor receptors; Gene mutations; Genes; Genetic analysis; Genetic aspects; Genomics; Malignant phyllodes tumor; Mammography; Medical prognosis; Medical research; Metastases; Metastasis; Molecular profiling; Mutation; Next-generation sequencing; p53 Protein; Pathogenicity; Patients; Polymorphism; Rare diseases; Surgery; Therapeutic targets; Tumors; Tyrosine; Germany; Kazakhstan
• ISSN: 1750-1172; 1750-1172
• DOI: 10.1186/s13023-021-01986-z

The genomic landscape of phyllodes tumors (PTs) of the breast is not well defined, especially in patients with advanced disease. To shed light on this topic, paired primary and progressed tumor samples from two patients with malignant PTs were subjected to next-generation sequencing (NGS) followed by functional analysis of genetic alterations using two prediction tools. The DNA of both the primary tumor and distant metastases of Patient 1 and the primary and recurrent tumor of Patient 2 were subjected to molecular profiling. NGS with the FoundationOne[R] assay was performed in a commercial molecular pathology laboratory. Two in silico prediction tools were used to estimate the pathogenicity of indicated genetic alterations. In total, 38 genomic alterations were detected, of which 11 were predicted to be probably benign. In Patient 1, 14 aberrations were identified in the primary tumor and 17 in pulmonary metastases, 12 of which were identical. In the primary and recurrent tumor of Patient 2, 17 and 15 sequence variants, respectively, were found, with 13 overlapping findings. Affected genes included seven (TP53, TERT, APC, ARID1A, EGFR, KMT2D, and RB1) of the top 10 most frequently altered genes in other advanced cancer entities, as well as four actionable therapeutic targets (EGFR, KIT, PDGFRA, and BRIP1). Of note, seven genes coding for receptor tyrosine kinases were affected: three in Patient 1 and four in Patient 2. Several genes (e.g. EPHA3, EPHA7, and EPHB1) were shown to be altered for the first time in PTs. The two progressed malignant PTs investigated here share some of the major genetic events occurring in other advanced cancers.