Table 2. Human tumors displaying genetic alterations in Hippo pathway components or in YAP/TAZ.

Affected gene	Consequence on YAP/TAZ enrichment	Functional Evidence
Human tumors displaying genetic alterations in Hippo pathway components
Malignant Mesothelioma (MM)
NF2 (19% inactivating mutations; 19% CNL; 7% inactivating fusions) STK4 (MST1; 16% CNL) SAV1 (12% CNL) LATS1 (20% CNL) LATS2 (1% inactivating mutations; 5% CNL) (reviewed in 4).	YAP staining is negative in normal pleural samples, but positive in 93% of MM samples203.	Mice develop MMs after combined ablation of Nf2 and Cdkn2a or Nf2 and Tp53 in mesothelial cells204. The development of asbestos-induced MMs is greatly accelerated in mice lacking one allele of Nf2205. YAP depletion inhibits the invasive and clonogenic abilities of H290 and H2052 NF2-mutant human MM cells203.
Sporadic Meningioma
NF2 (~45% inactivating mutations combined with LOH) (reviewed in 4)	YAP is highly expressed and localizes in the nucleus of tumor cells in 100% of human meningiomas of all grades106.	Patients with germline heterozygous mutation of NF2 develop neurofibromatosis type 2, which includes the development of meningiomas associated to LOH of NF2 206. In mice, biallelic loss of Nf2 in cells of the arachnoid leads to development of meningiomas207. YAP knockdown suppresses in vitro proliferation and migration of human meningioma cells106.
Sporadic Schwannoma
NF2 (77% inactivating mutations and/or CNL) ((reviewed in 4).	YAP is found in the nucleus of schwannoma cells in 100% of cases (reviewed in 42).	Patients with germline heterozygous mutation of NF2 develop neurofibromatosis type 2, which includes the development of schwannomas associated to LOH of NF2. 206 Mice with biallelic loss of Nf2 in Schwann cells develop manifestations of neurofibromatosis type 2, including development of schwannomas208.
Sporadic Spine-Ependymoma (SP-EPN)
NF2 (39% inactivating mutations) (reviewed in 4).		Patients with germline heterozygous mutation of NF2 develop neurofibromatosis type 2, which includes the development of ependymomas associated to LOH of NF2.206 In mice, loss of Lats1/2 in Neural Stem Cells (NSCs) induces formation of EPNs in a YAP/TAZ-dependent manner209.
Renal-Cell Carcinoma (RCC)
Papillary (pRCC): NF2 (6% inactivating mutations) SAV1 (3% inactivating mutations) (reviewed in 4) Sarcomatoid clear cell (sccRCC): NF2 (12% inactivating mutations) LATS2 (6% inactivating mutations)210 Mucinous tubular and spindle cell (mtscRCC): NF2 (23% biallelic inactivating mutations) SAV1 (4.5% biallelic inactivating mutations) PTPN14 (32% biallelic inactivating mutations)211.	YAP is found nuclear in 90% of mtscRCC cases211.	In mice, biallelic loss of Nf2 or deletion of both Lats1 and Lats2 in adult kidney epithelia induces formation of malignant RCCs212,213. NF2 reconstitution or YAP knockdown in NF2-deficient sccRCC cells restrains proliferation and invasion in vitro and tumor growth in vivo210.
Intrahepatic Cholangiocarcinoma (ICC)
SAV1 (~10% CNL) NF2 (9% inactivating mutations) (reviewed in 4)	YAP is found nuclear in 71% of ICC cases, and this is predictive of poor patient survival214.	In mice, homozygous knockout of Sav1 or Nf2 in liver cells causes biliary cell reaction, later developing in liver tumors, including ICCs. These events are rescued by concomitant deletion of Yap1. (reviewed in 42).
Human tumors displaying genetic alterations in YAP and/or TAZ (WWTR1)
Cervical Carcinoma
YAP1 (12-16% focal amplifications) WWTR1 (8% focal amplifications)75	YAP is weakly expressed by normal cervical tissue, but it is overexpressed by 91% of cervical carcinomas215.	Expression of transgenic YAP-S127A in the basal cells of the cervix induces development of invasive cervical carcinomas in mice215.
Head and Neck Squamous Cell Carcinoma (HNSCC)
YAP1 (6% focal amplifications) WWTR1 (9% focal amplifications) 75	TAZ is overexpressed and nuclear in 50% of oral HNSCC samples, and is predictive of poor patient survival (reviewed in 42).	YAP and TAZ are required for tumor formation by HNSCC cells transplanted in the orthotopic site (tongue) (reviewed in 42). YAP and TAZ are required for the fitness of distinct types of oral HNSCC cell lines, with TAZ being required in cells displaying amplification of WWTR1216
Esophageal Squamous Cell Carcinoma (ESCC)
YAP1 (6% focal amplifications) WWTR1 (27% focal amplifications) 75	60-90% of ESCC samples display nuclear YAP and TAZ staining. Nuclear expression of YAP is predictive of poor survival in ESCC patients (reviewed in 42).	YAP is required for proliferation of ESCC in vitro (reviewed in 42).
Ovarian Serous Cystadenocarcinoma (OV)
YAP1 (8% focal amplifications) 75	49% of OV display elevated expression of YAP, mostly in the nucleus217	Overexpression of YAP converts cells of the fallopian tube (the cells-of-origin of ovarian cancer) into high-grade serous carcer cells able to form tumors in vivo (reviewed in 42).
Hemangio-Endothelioma (HE)
Epithelioid (EHE): WWTR1 (~90% gene fusion with CAMTA1). YAP1 (8% gene fusion with TFE3) (reviewed in 79). Retinoid (RHE): YAP1 (38% fusion with MAML2) (reviewed in 79). Composite (CHE): YAP1 (27% fusion with MAML2) (reviewed in 79).	TAZ-CAMTA1 is found in the nucleus in ~90% of EHEs. 7% of EHEs display nuclear YAP-TFE3 (reviewed in 79).	Transgenic WWTR1-CAMTA1 expression in endothelial cells induces development of HE in mice77,78.
Supratentorial Ependymoma (ST-EPN)
YAP1 (5% gene fusions, 86% of which with MAMLD1, and 14% with FAM118B) (reviewed in 79).		Transgenic expression of the YAP-MAMLD1 or YAP-FAM118B in NSCs induces formation of ST-EPN in mice (reviewed in 79).
Poroma/Porocarcinoma
Poroma: YAP1 (20.2% fusion with NUTM1, 68.3% fusion with MAML2) WWTR1 (1% fusion with NUTM1) Porocarcinoma: YAP1 (54.6% fusion with NUTM1, 9.1% fusion with MAML2) (reviewed in 79).	Nuclear YAP/TAZ is detected in 96% of poromas and 64% of porocarcinomas (reviewed in 79).	YAP1-MAML2, YAP1-NUTM1, and WWTR1-NUTM1 can promote fibroblast transformation in soft agar assay (reviewed in 79).
Hybrid Low-grade Fibromyxoid Sarcoma/Sclerosing Epithelioid Fibrosarcoma
YAP1 (75% fusion with KMT2A) (reviewed in 79).