PALB2 and breast cancer: ready for clinical translation!

Figures & data

Figure 1 The structure of PALB2 indicating the exonic (exons 1–13) contribution to the protein and the location of the binding sites of its interacting proteins.

Abbreviation: ChAM, chromatin-association motif.

Table 1 PALB2 germline mutations and carrier frequencies

Populations	PALB2 mutations	Case–carrier frequency (%)	Control-carrier frequency (%)	Reference	Study designa
Australia	PALB2 c.196C >T, p.Gln66*	1/70 (1.4)	–	18	Familial breast cancer
		1/747 (0.1%)	–	36	Familial breast cancer
	PALB2 c.3113G >A, p.Trp1038*	1/70 (1.4)	–	18	Familial breast cancer
		5/1403 (0.004%)	0/764	17	Population-based
		2/66 (3%)		17	Early-onset multiple-case breast cancer
		8/871 (0.9%)	–	41	Familial breast cancer
		7/747 (0.9%)	–	36	Familial breast cancer
	PALB2 c.1947_1948 insA, p.Glu650fs*13	1/747 (0.1%)	–	36	Familial breast cancer
	PALB2 c.2982_2983 insT, p.Ala995fs*16	1/747 (0.1%)	–	36	Familial breast cancer
Canada	PALB2 c.229delT, p.Cys77fs*100	1/68 (1.5)	–	29	Familial breast cancer
	PALB2 c.2323C >T, p.Gln775*	3/406 (0.7)	0/6440	38	Early-onset and familial breast cancer
		1/71 (1.4)	–	70	Familial breast cancer
		1/491 (0.2)	–	70	Ovarian cancer cases
		1/564 (0.2)	0/6439	27	Early-onset breast cancer
	PALB2 c.3201_3561del, p.Met1067_Ser1186del	1/228 (0.4)	–	28	Pancreatic cancer cases
People’s Republic of China	PALB2 c.751C >T, p.Gln251*	2/360 (0.6)	0/864	19	Familial breast cancer
	PALB2 c.1050_1051delAAinsTCT, p.Gln350fs*11	1/360 (0.3)	0/864	19	Familial breast cancer
Finland	PALB2 c.1592delT, p.Leu531fs*30a	17/1918 (0.9)	6/2501 (0.2)	39,42	Population-based
		19/947 (2)	2/1079 (0.2)	40	Familial breast cancer
		8/1274 (0.6)		40	Sporadic breast cancer
Germany/Russia	PALB2 c.508­9delAG, p.Arg170fs*8	1/81 (1.2)	–	51	Pancreatic cancer familiesb
	PALB2 c.509_510delGA, p.Arg170fs*14	1/203 (0.49)	–	20	Bilateral breast cancer cases
	PALB2 c.758 insT, p.Leu273fs*4	1/40 (2.5)c	–	71	Triple negative breast cancer
	PALB2 c.1240C >T, p.Arg414*	1/203 (0.49)	–	20	Bilateral breast cancer cases
		1/81 (1.2)	–	51	Pancreatic cancer familiesb
	PALB2 c.1633G >T, p.Glu545*	1/203 (0.49)	–	20	Bilateral breast cancer cases
	PALB2 c.2761C >T, p.Gln921*	1/203 (0.49)	–	20	Bilateral breast cancer cases
	PALB2 c.3116delA, p.Asn1039fs*2	1/81 (1.2)	–	51	Pancreatic cancer familiesb
Italy	PALB2 c.72delG, p.Leu24fs*9	1/62 (1.6)	–	21	Breast–pancreatic cancer families
	PALB2 c.1027C >T, p.Gln343*	1/62 (1.6)	–	21	Breast–pancreatic cancer families
	PALB2 c.1317delG, p.Gly439fs*13	1/95 (1.0)	–	22	Familial breast cancer
	PALB2 c.2257C >T, p.Arg753*	1/132 (0.8)	0/300	23	Familial breast cancer
	PALB2 c.3497delG, p.Gly1166fs*21	1/62 (1.6)	–	21	Breast–pancreatic cancer families
Netherlands	PALB2 c.509_510delGA, p.Arg170fs*14	1/110 (1)d	–	24	Breast (including male)–pancreatic cancer families
Poland	PALB2 c.509_510delGA, p.Arg170fs*14	2/339 (0.6)	1/1310 (0.08)	31	Ovarian cancer cases
		4/648 (0.6)		31	Familial breast cancer
South Africa	PALB2 c.697delG, p.Val233fs*5	1/48 (2.0)	0/75	32	Unselected early-onset breast cancer
Spain	PALB2 c.1056_1057delGA, p.Glu352fs*8	1/797 (0.12)	–	33	Familial breast cancer
United Kingdom	PALB2 c.2386G >T, p.Gly796*	1/923 (0.1)	0/1084	2	Familial breast cancer
	PALB2 c.2982_2983 insT, p.Ala995fs*16	1/923 (0.1)	0/1084	2	Familial breast cancer
	PALB2 c.3113G >A, p.Trp1038*	2/923 (0.2)	0/1084	2	Familial breast cancer
	PALB2 c.3116delA, p.Asn1039fs*2	3/923 (0.3)	0/1084	2	Familial breast cancer
	PALB2 c.3549C >G, p.Tyr1183*	3/923 (0.3)	0/1084	2	Familial breast cancer
USA	PALB2 c.172_175delTTGT, p.Leu58fs*10	1/972 (0.1)	0/960	29	Familial breast cancer
	PALB2 c.196C > T, p.Gln66*	2/972 (0.2)	0/960	29	Familial breast cancer
	PALB2 c.509_510delGA, p.Arg170fs*14	7/972 (0.7)	0/960	29	Familial breast cancer
	PALB2 c.757_758delCT, p.Leu253fs*3	4/972 (0.4)	0/960	29	Familial breast cancer
	PALB2 c.1240C >T, p.Arg414*	3/972 (0.3)	0/960	29	Familial breast cancer
	PALB2 c.1592delT, p.Leu531fs*30a	1/559 (0.2)	0/565e	36	Contralateral breast cancer cases
	PALB2 c.1653T >A, p.Tyr551*	1/972 (0.1)	0/960	29	Familial breast cancer
	PALB2 c.2386G >T, p.Gly796*	1/972 (0.1)	0/960	29	Familial breast cancer
	PALB2 c.2559C >T, p.Gly853fs*21f	1/972 (0.1)	0/960	29	Familial breast cancer
	PALB2 c.2686_2987 insT, p.Ser896fs*32	3/972 (0.3)	0/960	29	Familial breast cancer
	PALB2 c.2718G >A, p.Trp906*	1/972 (0.1)	0/960	29	Familial breast cancer
	PALB2 c.2835­1G >C	1/559 (0.2)	0/565e	36	Contralateral breast cancer cases
	PALB2 c.2920_2921delAA, p.Lys974fs*5	1/972 (0.1)	0/960	29	Familial breast cancer
	PALB2 c.3026delC, p.Pro1009fs*6	2/972 (0.2)	0/960	29	Familial breast cancer
	PALB2 c.3113G >A, p.Trp1038*	5/972 (0.5)	0/960	29	Familial breast cancer
		1/559 (0.2)	0/565e	36	Contralateral breast cancer cases
	PALB2 c.3202 + 1G >C	1/559 (0.2)	0/565e	36	Contralateral breast cancer cases
	PALB2 c.3549C >G, p.Tyr1183*	1/94 (1)	–	30	Breast–pancreatic cancer families
		1/559 (0.2)	0/565e	36	Contralateral breast cancer cases
		1/97 (1)	–	24	Male breast cancer cases
	PALB2 c.2962C >T, p.Gln988*	1/94 (1)	–	30	Breast–pancreatic cancer families

Notes:

a Guide only, see reference for full details

b study includes EUROPAC

c carrier also BRCA1 mutation carrier

d carrier is a male breast cancer case

e controls are unilateral breast cancer case

f mutation identified via reverse transcription PCR.

Abbreviations: EUROPAC, The European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer; PCR, polymerase chain reaction.