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

Abstract

Background 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. Methods 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® assay was performed in a commercial molecular pathology laboratory. Two in silico prediction tools were used to estimate the pathogenicity of indicated genetic alterations. Results 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. Conclusions The two progressed malignant PTs investigated here share some of the major genetic events occurring in other advanced cancers.

Genomic characteristics of two breast malignant phyllodes tumors during pregnancy and lactation identified through whole-exome sequencing

“…phred Specific alteration Other alterations Type of tissue ATM NM_000051.3 + Missense variant p. P2901T Uncertain significance 1 0 Deleterious 1 D 32 Deleterious VUS One case, non- syn. SNV [ 29 ] NR M PT AXIN2 NM_004655.4 + Missense variant p. T227N Uncertain significance 1 0.003 Deleterious 0.989 D 25.1 Deleterious VUS NR NR BAP1 NM_004656.4 + Missense variant p. D107E Uncertain significance 1 0.459 Tolerated 0.015 B 10.98 Tolerated VUS NR NR NOTCH1 NM_017617.5 + + Missense variant p. A1418T Uncertain significance 1 0.248 Tolerated 0.014 B 15.54 Deleterious VUS NR …”