Sarcoma

Review Article

Targeting the p53 Pathway in Ewing Sarcoma

Table 2

TP53 Mutations in sarcomas other than ESFTs confirmed by DNA sequencing.


Sarcoma type	Study	Method	Exons sequenced	Mutation frequency	TP53 mutation

Liposarcoma
Well-differentiated/de-differentiated liposarcoma (WD/DDLPS)	Pilotti et al., 1997 [18]	IHC PCR-SSCP Sequencing	5–9	4/13	H179Y, R213(STOP) R282W, GgGc (SS)
	Dei Tos et al., 1997 [19]	IHC PCR-SSCP Sequencing	5–8	1/14	S127F
	Schneider-Stock et al., 1998 [20]	PCR-SSCP Sequencing	4–8	0/8	—
	Schneider-Stock et al., 1999 [21]	IHC PCR-SSCP Sequencing	5–8	0/13	—
	Barretina et al., 2010 [22]	Sequencing, mass spectrometry-based genotyping	—	0/50	—

				Total TP53 mutations	5/98 (5.1%)

Myxoid/Round cell liposarcoma	Pilotti et al., 1997 [18]	IHC PCR-SSCP Sequencing	5–9	1/6	Del nts 1506-1507 (STOP)
	Schneider-Stock et al., 1998 [20]	PCR-SSCP Sequencing	4–8	1/12	P128S
	Schneider-Stock et al., 1999 [21]	IHC PCR-SSCP Sequencing	5–8	3/19	H214L, P250T, G245S
	Oda et al., 2005 [23]	IHC PCR-SSCP Sequencing	5–9	5/77	Q167(STOP), H214Y V225A, C238Y, C242Y
	Barretina et al., 2010 [22]	Sequencing, mass spectrometry-based genotyping	—	0/21	—

				Total TP53 Mutations	10/135 (7.4%)

Pleomorphic liposarcoma	Schneider-Stock et al., 1998 [20]	PCR-SSCP Sequencing	4–8	3/6	R248Q, E271(STOP) R273C
	Schneider-Stock et al., 1999 [21]	IHC PCR-SSCP Sequencing	5–8	2/9	R248Q, R273C
	Barretina et al., 2010 [22]	Mass spectrometry-based genotyping	—	4/24	C135F, T155I CTT (SS), CCT (SS)

				Total TP53 mutations	9/39 (23.1%)

Undefined liposarcomas	Toguchida et al., 1992 [24]	PCR-SSCP Sequencing	2–11	1/4	AGgt>AGtt (SS)
	Leach et al., 1993 [38]	IHC Sequencing	5–8	3/13	Q144(STOP), N239S GGTGAT (SS)
	Latres et al., 1994 [25]	PCR-SSCP Sequencing	2–9	5/25	H168R, H193Y, M246V R248W, 344(STOP)
	Castresana et al., 1995 [26]	PCR-SSCP Sequencing	5–8	1/4	V216A
	Nawa et al., 1999 [27]	PCR-SSCP Sequencing	5–8	1/9	T253A
	Das et al., 2007 [28]	IHC Sequencing	2–11	1/3	377(FS)

				Total TP53 mutations	12/58 (20.7%)

Total TP53 mutations in liposarcomas					36/330 (10.9%)

Rhabdomyosarcoma	Felix et al., 1992 [29]	PCR-SSCP Sequencing	4–8	1/6	R213P
	Toguchida et al., 1992 [24]	PCR-SSCP Sequencing	2–11	0/4	—
	Latres et al., 1994 [25]	PCR-SSCP Sequencing	2–9	0/2	—
	Castresana et al., 1995 [26]	PCR-SSCP Sequencing	5–8	1/1	V218L
	Kusafuka et al., 1997 [30]	PCR-SSCP Sequencing	5–8	1/10	R273H
	Nawa et al., 1999 [27]	PCR-SSCP Sequencing	5–8	0/2	—
	Taylor et al., 2000 [31]	PCR-SSCP Sequencing	5–9	1/20	Del nt 1004-1017
	Takahashi et al., 2004 [32]	PCR-SSCP Sequencing	5–9	9/45	E204G, R209T, P223R M243T, G245C, N247D, R249G, C291Q, P295H
	Das et al., 2007 [28]	IHC Sequencing	2–11	1/4	D393N

Total TP53 mutations in rhabdomyosarcomas					14/94 (14.9%)

Synovial Sarcoma	Toguchida et al., 1992 [24]	PCR-SSCP Sequencing	2–11	0/5	—
	Latres et al., 1994 [25]	PCR-SSCP Sequencing	2–9	0/8	—
	Schneider-Stock et al., 1997 [33]	IHC PCR-SSCP Sequencing	5–8	0/2	—
	Dei Tos et al., 1999 [34]	PCR-SSCP Sequencing	—	4/20	Not Specified
	Nawa et al., 1999 [27]	PCR-SSCP Sequencing	5–8	1/7	L194F
	Schneider-Stock et al., 1999 [35]	IHC PCR-SSCP Sequencing	5–8	2/19	P128L, R248W
	Oda et al., 2000 [36]	IHC PCR-SSCP Sequencing	5–9	9/49	C141Y, A159T,V173M I195F, R196Q, G199R R213(STOP), N235D C238Y
	Das et al., 2007 [28]	IHC Sequencing	2–11	5/7	9(STOP), A63P, S96C, P250T, P250T
	Barretina et al., 2010 [22]	Sequencing, mass spectrometry-based genotyping	—	0/23	—

Total TP53 mutations in Synovial Sarcomas					21/140 (15.0%)

Malignant Fibrous Histiocytoma	Toguchida et al., 1992 [24]	PCR-SSCP Sequencing	2–11	2/13	R196(STOP), R273H
	Andreassen et al., 1993 [37]	CDGE Sequencing	5,7,8	3/12	V143M, Y163C, G244D
	Leach et al., 1993 [38]	IHC Sequencing	5–8	1/11	R158H
	Latres et al., 1994[25]	PCR-SSCP Sequencing	2–9	0/9	—
	Castresana et al., 1995 [26]	PCR-SSCP Sequencing	5–8	3/12	Not Specified
	Schneider-Stock et al., 1997 [33]	IHC PCR-SSCP Sequencing	5–8	2/15	Y220C, C277(STOP)
	Nawa et al., 1999[27]	PCR-SSCP Sequencing	5–8	5/15	Y126F, R175H R213(STOP), S241T R248Q
	Das et al., 2007 [28]	IHC Sequencing	2–11	2/11	P77Q, 213(FS)

Total TP53 mutations in malignant fibrous histiocytoma					18/98 (18.4%)

Leiomyosarcoma	Andreassen et al., 1993 [37]	CDGE Sequencing	5,7,8	2/6	K132M, R248W
	Latres et al., 1994[25]	PCR-SSCP Sequencing	2–9	5/13	Y163C, Y163C, H214R, G266E, ATgg>ATag (SS Intron 5)
	Patterson et al., 1994 [39]	PCR-SSCP Sequencing	4–9	6/29	P151H, P152L, R158H V216M, C238F, V272M
	Castresana et al., 1995 [26]	PCR-SSCP Sequencing	5–8	1/1	Not Specified
	Miller et al., 1996 [40]	PCR-SSCP Sequencing	2–11	1/8	Q165(STOP)
	Hall et al., 1997 [41]	IHC PCR-SSCP Sequencing	5–8	3/21	K163E, T211I A nt Del codon 246
	Schneider-Stock et al., 1997 [33]	IHC PCR-SSCP Sequencing	5–8	0/7	—
	Nawa et al., 1999[27]	PCR-SSCP Sequencing	5–8	0/3	—
	Zhai et al., 1999 [42]	IHC Sequencing	5–8	9/21	V173M, Y205C, S215R, R248Q, R249W, R273H, A276D, E285D, S303I
	Miyajima et al., 2001 [43]	IHC PCR-SSCP Sequencing	5–9	8/13	A161T, D184N, T220C T220C, C238S, C238C R273H, G279V
	Das et al., 2007 [28]	IHC Sequencing	2–11	0/5	—
	Barretina et al., 2010 [22]	Sequencing, mass spectrometry-based genotyping	—	0/27	—

Total TP53 mutations in leiomyosarcomas					35/154 (22.7%)

Osteosarcoma	Toguchida et al., 1992 [24]	PCR-SSCP Sequencing	2–11	14/76	46 (STOP), 112 (STOP), R175H H193Q, E221(STOP) 227(STOP), S241Y G244V, P250L, D259V R273H, D281H, D281N aaTG > ggTCG (SS)
	Andreassen et al., 1993 [37]	CDGE Sequencing	5, 7, 8	2/11	D281E, E286K
	Castresana et al., 1995 [26]	PCR-SSCP Sequencing	5–8	2/7	169(STOP), D281Y
	Miller et al., 1996 [40]	PCR-SSCP Sequencing	2–11	13/42	H179Y, E224D, 239(FS), G245D, R248W, R248, 248(FS), R273H R273H, A276P R282Q, R282Q R282H
	Patiño-García and Sierrasesúmaga, 1997 [8]	PCR-DDGE Sequencing	5–8	6/37	R175H, R196(STOP) P250F, N268S, R273H R2735
	Gokgoz et al., 2001 [44]	PCR-SCCP Sequencing	4–10	60/272	agTCC > aaTCC (SS) L43(STOP), L43(STOP), P47L, 73(FS), 73(FS), 83(FS), 83(FS) In-Frame Ins (GGT) Codon 107/108 ACGgt/ACGtt(SS), agTAC/aaTAC (SS), V172D, R175H ATGgt/ATGat(SS), R181P, R196(STOP) V197G, Del codon 202–206, E204(STOP), Y205C R213(STOP), Y220C Y220C, E221(STOP) 31bp Del (FS) Intron 6 to Exon 7 229(FS), M237I, M237I, M237I, C238GC238G, C238G 241(FS), C242Y, C242Y, G245S, G245S R248W, R248Q, R248Q, R248Q, R248Q, P250L, T256S 15 bp In-frame Del (codon 265) R273H, R273H, R273H, R280H, D281H, D281H D281N, D281N E285K, Del codon 296–303 298(FS) GAGgt/GAGct (SS) R337C, R342(STOP) E343(STOP)
	Overholtzer et al., 2003 [45]	PCR-SCCP PCR-LDR	5–8	12/32	V173G, V173M, R175H, Del codon 175, Y220C, E224D, V272M, R273H, R273C, D281H FS (Exon 6), FS (Del 17nt) Exon 5

Total TP53 mutations in osteosarcomas					109/477 (22.9%)

CDGE: Constant Denaturant Gel Electrophoresis; DDGE: Denaturing Gradient Gel Electrophoresis; IHC: Immunohistochemistry; PCR-SSCP: Polymerase Chain Reaction Single-Strand Conformational Polymorphism; PCR-LDR: Polymerase Chain Reaction Ligase-Detection Reaction; FS: Frame shift; Del: Deletion; Ins: Insertion; SS: Splice Site. Mutations in bold indicate p53 “hotspot mutations’’. Recurrences with TP53 mutations have been omitted in studies that reported both the primary tumour and recurrence with the same mutation.