Supplementary Table 1. MET copy number variation Real-time PCR primers

Target / Name / Sequence / Product size
MET / MET_cnv_F / ATTGGTGATTGCTTGGGTAGTT / 63bp
MET_cnv_R / CCTGTGGGTTTACTTTGGTTG
Reference / ALB_cnv_F / TGAAACATACGTTCCCAAAGAGTTT / 81bp
ALB_cnv_R / CTCTCCTTCTCAGAAAGTGTGCATAT

Supplementary Table 2. MET skipping-specific Real-time PCR primers

Target / Name / Sequence / Site / Product size
Total MET / MET_t_F / ACTGTGCTGTGAAATCCTTG / MET ex16 / 75 bp
MET_t_R / TGATGATTCCCTCGGTCAGAA / MET ex17
Wt MET / MET_wt_F / AGACTACCGAGCTACTTTTCCA / MET ex14 / 80 bp
MET_wt_R / GAGGATACTGCACTTGTCGG / MET ex15
Del MET / MET_del_F / AAAGAGAAAGCAAATTAAAGATCAGT / MET ex13-15 span / 65 bp
MET_del_R / GCACTTGTCGGCATGAACC / MET ex15
Reference / GUSB_F / CTCATTTGGAATTTTGCCGATT / 81bp
GUSB_R / CCGAGTGAAGATCCCCTTTTTA

Supplementary Table 3. METex14splicing sites sequencing primer

Target / Name / Sequence / Product size
Splice acceptor / MET_5u_F / GTGCATTTTTGTTACTGTTCATTTTT / 230bp
MET_5u_R / CTCTTGCATCGTAGCGAACTAAT
Splice donor / MET_3d_F / TGTAAGTGCCCGAAGTGTAAG / 206bp
MET_3d_R / GCAGAGGTAAATACTTCCTTTAGGTTT

Supplementary Table 4. Screening of METex14 skipping specific siRNA sequences

Name / Sequence
01 / AGATCAGTTTCCTAATTCA
02 / AAGATCAGTTTCCTAATTC
03 / AAAGATCAGTTTCCTAATT
04 / TAAAGATCAGTTTCCTAAT
05 / TTAAAGATCAGTTTCCTAA
06 / ATTAAAGATCAGTTTCCTA
07 / AATTAAAGATCAGTTTCCT
08 / AAATTAAAGATCAGTTTCC
09 / CAAATTAAAGATCAGTTTC
10 / GCAAATTAAAGATCAGTTT
11 / AGCAAATTAAAGATCAGTT
12 / AAGCAAATTAAAGATCAGT
13 / AAAGCAAATTAAAGATCAG
14 / GAAAGCAAATTAAAGATCA

Supplementary Table 5.Clinicopathologic details of 17 patients with lung adenocarcinoma harboring METex14 skipping

No. / Sex / Age / Smoking / Preop. therapy / Surgery / pT / pN / pM / pStage / Diff / Predominant growth pattern / IHC / Postop. CTx / Postop. RTx / F/U duration / Recurrence / Death
MET mem / MET cyt / HGF / p53 / MDM2
1 / M / 73 / Former / No / Segmentectomy / 2a / 0 / 0 / 1B / MD / acinar / 3+ / 2+ / 2+ / - / 1+, 30% / Yes / No / 71 / Yes / No
2 / F / 73 / Never / No / Lobectomy / 2a / 0 / 0 / 1B / MD / acinar / 2+ / 2+ / 2+ / - / 1+, 10% / No / No / 5 / No / No
3 / M / 78 / Former / No / Lobectomy / 4 / 0 / 0 / 3A / WD / acinar / 2+ / 2+ / 2+ / - / 2+, 70% / No / No / 57 / No / No
4 / M / 73 / Former / No / Bilobectomy / 4 / 1 / 0 / 3A / PD / solid / 2+ / 2+ / 1+ / - / 1+, 20% / Yes / Yes / 36 / Yes / Yes
5 / F / 79 / Current / No / Lobectomy / 2a / 2 / 0 / 3A / PD / solid / 3+ / 2+ / 1+* / - / 2+, 60% / No / Yes / 32 / Yes / No
6 / M / 74 / Former / No / Sleeve lobectomy / 4 / 0 / 0 / 3A / MD / acinar / 3+ / 2+ / 2+* / - / 0 / Yes / Yes / 18 / Yes / No
7 / F / 81 / Never / No / Lobectomy / 2a / 0 / 0 / 1B / MD / acinar / 3+ / 2+ / 2+ / + / 3+, 80% / Yes / No / 23 / Yes / Yes
8 / F / 55 / Never / No / Lobectomy / 1a / 0 / 0 / 1A / MD / acinar / 3+ / 2+ / 2+ / + / 2+, 10% / No / No / 17 / No / No
9 / M / 55 / Former / No / Lobectomy / 1b / 0 / 0 / 1A / MD / papillary / 3+ / 3+ / 2+ / - / 2+, 80% / No / No / 59 / No / No
10 / M / 75 / Current / No / Lobectomy / 2a / 0 / 0 / 1B / PD / solid / 3+ / 3+ / 2+* / - / 0 / No / No / 25 / Yes / No
11 / M / 80 / Current / No / Segmentectomy / 3 / 0 / 0 / 2B / PD / solid / 3+ / 3+ / 2+ / - / 2+, 30% / Yes / No / 52 / Yes / No
12 / M / 63 / Former / No / Lobectomy / 2a / 0 / 0 / 1B / PD / solid / 3+ / 3+ / 2+* / - / 3+, 50% / Yes / No / 48 / No / No
13 / M / 70 / Former / No / Lobectomy / 2a / 2 / 0 / 3A / PD / solid / 3+ / 3+ / 2+ / - / 3+, 60% / Yes / Yes / 17 / Yes / No
14 / F / 78 / Never / No / Lobectomy / 2b / 0 / 0 / 2A / MD / papillary / 3+ / 3+ / 2+ / - / 2+, 20% / No / No / 3 / No / No
15 / F / 66 / Never / No / Lobectomy / 2b / 0 / 0 / 2A / MD / acinar / 3+ / 3+ / 2+ / - / 0 / Yes / No / 16 / No / No
16 / F / 65 / Never / No / Lobectomy / 2a / 0 / 0 / 1B / MD / acinar / NA / NA / NA / NA / NA / Yes / No / 34 / Yes / No
17 / F / 69 / Never / No / Lobectomy / 2a / 0 / 0 / 1B / MD / acinar / NA / NA / NA / NA / NA / No / No / 39 / Yes / No

pT, pathologic T status; pN, pathologic N status; pM, pathologic M status; pStage, pathologic stage;Diff, differentiation; mem, membranous; cyt, cytoplasmic; IHC, immuonohistochemicalstain;CTx, chemotherapy; RTx, radiation therapy;F/U, follow-up; M, male; F, female;; MD, moderately differentiated; PD, poorly differentiated; NA, not assessed.

* : positive of tumor and stromal cells

Supplementary Table 6.Immunohistochemical results according to METex14 skippingstatus

Number of patients / METex14 skipping (+) / METex14 skipping (-) / p-value
MET (n=42) / <0.001
Negative / 19 (45.2%) / 0 (0%) / 19 (70.4%)
Positive* / 23 (54.8%) / 15 (100%) / 8 (29.6%)
HGF (n=33) / 0.665
1+ / 6 (18.2%) / 2 (13.3%) / 4 (22.2%)
2+ / 27 (81.8%) / 13 (86.7%) / 14 (77.8%)
MDM2 (n=31) / 0.073
Negative / 18 (58.1%) / 6 (40.0%) / 12 (75.0%)
Positive / 13 (41.9%) / 9 (60.0%) / 4 (25.0%)
p53 (n=33) / 1.000
Negative / 29 (87.9%) / 13 (86.7%) / 16 (88.9%)
Positive / 4 (12.1%) / 2 (13.3%) / 2 (11.1%)

*:cytoplasm ≥2+ or membrane ≥3+

Supplementary Table 7. Molecular details of 17 patients with lung adenocarcinoma harboring METex14 skipping

No. / CNV / Del_per_GUSB_ratio / MET_per_GUSB_ratio / MET mutation type
1 / 1.44 / 0.45 / 0.54 / NA
2 / 1.07 / 0.37 / 0.46 / c.2888-23_2890delinsCCCCT
3 / 0.96 / 0.41 / 0.72 / c.3028+1G>A
4 / 1.32 / 1.09 / 0.89 / NA
5 / 1.22 / 2.97 / 3.95 / c.3028G>T
6 / 0.9 / 0.29 / 0.41 / c.3028+2T>G
7 / 0.76 / 0.65 / 1.16 / NA
8 / 1.11 / 0.23 / 0.69 / c.3028+1G>A
9 / 1.45 / 0.53 / 0.6 / c.2888-27_2888-10delAAGCTCTTTCTTTCTCTC
10 / 0.96 / 4.6 / 6.01 / c.2888-18_2888-1delCTTTCTCTCTGTTTTAAG
11 / 1.28 / 1.87 / 3.56 / c.2888-22_2888-6delCTTTCTTTCTCTCTGTT
12 / 1.02 / 4.3 / 5.83 / c.3028+3_2082+12delATATTTCAGT
13 / 1.94 / 3.32 / 5.68 / c.3028+1G>T
14 / 1.26 / 0.34 / 0.77 / c.2888-38_2888-20delCCGTCTTTAACAAGCTCTT
15 / 1.1 / 0.06 / 0.19 / c.2888-20_2888-10delTTCTTTCTCTC
16 / NA / 0.3 / 0.47 / NA
17 / 1.48 / 0.23 / 0.32 / NA

CNV, copy number variation; NA, not assessed.