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

Table 2 Variants of unknown significance identified in the primary tumor (P1) and lung metastasis (M1) of Patient 1 as well as the primary (P2) and recurrent tumor (R2) of Patient 2

Gene	Type of alteration		Patient		Prediction of functional consequences		Occurrence of genomic alterations previously reported in PTs
Gene	General classification	Details	1	2	FATHMM-XF	MutationTaster2	Specific alteration	Other alterations	Type of tissue
EPHA3	non-syn. SNV	p.K713T	P1, M1		0.30, benign	Disease causing	NR	NR
EPHA7	non-syn. SNV	p.T118A	M1		0.13, benign¹	Disease causing	NR	NR
EPHB1	non-syn. SNV	p.R637H	P1, M1		0.06, benign¹	Disease causing	NR	NR
GRM3	non-syn. SNV	p. N516S		P2, R2	NA	Disease causing	NR	NR
MAF	non-syn. SNV	p.L138M	P1		0.07, benign	Polymorphism	NR	NR
MST1R	non-syn. SNV	p.R470H		P2, R2	0.06, benign¹	Disease causing	NR	NR
NTRK3	non-syn. SNV	p.S564C	P1, M1		0.02, benign high confidence	Polymorphism	NR	NR
PRKN (PARK2)	non-syn. SNV	p.R442G		P2, R2	0.03, benign	Polymorphism	NR	NR
PIK3C2G	non-syn. SNV	p.H1274D		P2, R2	NA	Disease causing	NR	One case, non-syn. SNV [29]	metastatic malignant
PLCG2	non-syn. SNV	p.T961M	M1		NA	Disease causing	NR	NR
SPTA1	non-syn. SNV	p.R885H	M1		NA	Polymorphism	NR	NR
ZNF703	fs deletion, stop gain mutation	p.G22fs*50	P1, M1		–	Disease causing	NR	Three cases [18]	P, R: benign, malignant

fs, frameshift; non-syn. SNV, non-synonymous single-nucleotide variant; NA, not available; NR, not reported; P, primary tumor; PT, phyllodes tumor; R, recurrence; M, distant metastases; *, stop codon
¹According to the COSMIC database (cancer.sanger.ac.uk) [22], the FATHMM-MKL prediction was pathogenic for EPHA7 (score: 0.94), EPHB1 (score: 0.99), and MST1R (score: 0.95)

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