Table 2.

Summary of BAP1 gene alterations in malignant mesothelioma

Histological type	Specimen	Source	Allelic status of 3p21.1 (position: 52.4–52.6 Mb)	Genomic alterations in BAP1		BAP1 expression
				Mutation in the coding region	Somatic alteration	mRNA	Protein	Nuclear immunostaining in tumor tissue
Epithelioid	MM19‐P	HCM	−/+	Deletion of BAP1 coding region	+	−	−	−
	MM21‐P	HCM	−/−	Deletion of entire BAP1 gene	+	−	−	−
	MM26‐P	HCM	+/+	ND	−	++	++	+
	MM34‐P†	HCM	−/−	Deletion of entire BAP1 gene	+	−	N/A	N/A
	MM35‐P	HCM	−/+	Nonsense mutation at aa 460 (g.52437782C>G, p.S460X)	+	±	−	−
	MM39‐P	HCM	−/+	Deletion of exons 1–5	N/A	−	−	−
	MM45‐P	HCM	−/+	ND	+	+	N/A	−
	MM48‐P	HCM	−/+	Deletion of exons 1–5	+	−	−	−
	MM56‐P	HCM	−/+	Frameshift mutation at aa146(g.52441416delAinsCG, p.R146RfsX9)	N/A	±	−	−‡
	MM57‐P	HCM	−/+	Deletion of exons 10–17	+	−	N/A	−
	MM67‐P	HCM	+/+	ND	−	+	N/A	++
	MM14‐T	HCM	−/−	Deletion of entire BAP1 gene	+	N/A	N/A	−
	MM29‐T	HCM	−/+	3‐bp deletion at aa234 (g.52440352_52440350del, p.V234del)	+	N/A	N/A	−
	H28	ATCC	+/+	23‐bp deletion at intron 6/exon7 junction§ (g.52441351_52441329del)	N/A	++	N/A	N/A
	H2452	ATCC	−/+	Missense mutation at aa95 (g.52442065C>A, p.A95D)	N/A	++	−	N/A
	HMMME	RIKEN	−/+	19‐bp deletion (g.52441321_52441303del, p.R150RfsX31)	N/A	+	N/A	N/A
Non‐epithelioid (biphasic)	MM16‐P	HCM	+/+	ND	−	++	++	+
	MM30‐P	HCM	+/+	ND	−	++	+	+
	MM62‐P	HCM	+/+	Missense mutation at aa 173§ (g.52441252A>C, p.Y173S)	N/A	++	N/A	−
	MM80‐P	HCM	+/+	ND	−	++	N/A	+
	MSTO‐211H	ATCC	+/+	ND	−	+	N/A	N/A
Non‐epithelioid (sarcomatoid)	MM46‐P	HCM	+/+	ND	−	++	++	+
	H2052	ATCC	+/+	ND	−	++	N/A	N/A

†This specimen was unavailable for protein analysis. ‡Nuclear staining was seen in some tumor cells, but not all. §This was identified as a homozygous mutation without allelic loss by direct sequencing. The allelic status of 3p21.1 (position: 52.4–52.6 Mb), identified from our previously published Comparative Genomic Hybridization (CGH) array data,10 is shown, and biallelic and monoallelic deletion of this region is indicated by −/− and −/+, respectively. Mutations in the BAP1 coding region were identified by direct sequencing of 10 fragments, derived from the entire coding region of this gene and amplified using the primers described in Table 1. For somatic alterations, the “+” indicates mutations judged to be of somatic origin of the nine malignant mesotheliomas (MMs) for which comparisons with paired non‐tumor DNA were possible and “−” indicates no mutations in the coding region. For BAP1 expression, expression level data summarized from Figure 3 are shown as – (no expression), ±, +, or ++ (similar as that in Met5a cells). Immunohistochemistry was performed using a anti‐BAP1 antibody for primary tissue specimens and nuclear immunostaining is indicates as −, +, and ++ (similar as that in non‐tumor mesothelial cells shown in Fig. 4a). aa, amino acid; HCM, Hyogo College of Medicine; ND, not detected; N/A, not analyzed.