Table 1.
Clinicopathologic and molecular features of 29 YAP1–KMT2A fusion-positive sarcomas, including 16 from this study (patient cases #1–16) and 13 from prior reports (patient cases #17–29).
| Patient no. | Age/gender | Primary location (sequenced site if different) | Position of fusion (5′–3′) breakpoint 1 | Position of fusion (5′–3′) breakpoint 2 | Concurrent KMT2A exon-level deletion | Concurrent genomic alterations | Molecular assay/sequencing method (prior reference, if applicable) |
|---|---|---|---|---|---|---|---|
| 1 | 42/F | Abdomen | Not evaluated | KMT2A exon 6 to YAP1 exon 9 | Not evaluated | None | MGH fusion, MGH snapshot |
| 2 | 35/F | Unknown (lung) | YAP1 exon 5 to KMT2A exon 4 | KMT2A exon 6 to YAP1 exon 9 | Not detected | CDKN2A homozygous loss, STAG2 p.R953*, PTEN p.D92N, PASK c.3814+1G>A | FoundationOne Heme® |
| 3 | 60/F | Abdomen | YAP1 exon 5 to KMT2A exon 4 | KMT2A exon 6 to YAP1 exon 9 | Not detected | None | FoundationOne Heme® |
| 4 | 31/F | Retroperitoneum | YAP1 exon 5 to KMT2A exon 4 | KMT2A exon 6 to YAP1 exon 9 | Not detected | RB1 homozygous loss | FoundationOne Heme® |
| 5 | 66/F | Scalp | YAP1 exon 5 to KMT2A exon 4 | KMT2A exon 6 to YAP1 exon 9 | Exons 4–6 (DNA and RNA) | Homozygous loss of CDKN2A and CD58 | FoundationOne Heme® |
| 6 | 47/M | Chest | YAP1 exon 5 to KMT2A exon 4 | KMT2A exon 6 to YAP1 exon 9 | Exons 4–28 (RNA only) | CDKN2A homozygous loss | FoundationOne Heme® |
| 7 | 63/F | Abdomen | YAP1 exon 5 to KMT2A exon 4 | KMT2A exon 6 to YAP1 exon 9 | Exons 4–6 (RNA only) | Amplification of MDM2 and PMI1, CDKN2A homozygous loss | FoundationOne Heme® |
| 8 | 33/M | Back (right axilla) | YAP1 exon 5 to KMT2A exon 4 | KMT2A exon 6 to YAP1 exon 9 | Exons 4–6 (DNA and RNA) | None | FoundationOne Heme® |
| 9 | 29/M | Right leg (thoracic spine) | YAP1 exon 5 to KMT2A exon 4 | KMT2A exon 6 to YAP1 exon 9 | Exons 4–26 (DNA and RNA) | CDKN2A homozygous loss, FLCN p.W306* | FoundationOne Heme® |
| 10 | 32/F | Left thigh | YAP1 exon 5 to KMT2A exon 4 | KMT2A exon 6 to YAP1 exon 9 | Not detected | Amplification of MDM4, IKBKE, and MCL1 | FoundationOne Heme® |
| 11 | 20/F | Unknown (pleura) | YAP1 exon 5 to KMT2A exon 4 | KMT2A exon 6 to YAP1 exon 9 | Exons 4–6 (DNA and RNA) | CDKN2A homozygous loss, ZNF703 amplification | FoundationOne Heme® |
| 12 | 64/F | Left hand (lung) | YAP1 exon 5 to KMT2A exon 4 | KMT2A exon 6 to YAP1 exon 9 | Exons 4–6 (RNA only) | CD36 p.V263fs*16 | FoundationOne Heme® |
| 13 | 38/M | Left hip (pleura) | YAP1 exon 5 to KMT2A exon 4 | KMT2A exon 6 to YAP1 exon 9 | Exons 4–6 (DNA and RNA) | CDKN2A homozygous loss | FoundationOne Heme® |
| 14 | 30/F | Peritoneum (right shoulder) | YAP1 exon 5 to KMT2A exon 4 | KMT2A exon 6 to YAP1 exon 9 | Not detected | Homozygous loss of CDKN2A and RB1, ATR duplication intron 15—exon 20 | FoundationOne Heme® |
| 15 | 54/M | Right buttock (lung) | YAP1 exon 3 to KMT2A exon 5 | KMT2A exon 6 to YAP1 exon 5 | Exons 5–6 (DNA and RNA) | None | FoundationOne Heme® |
| 16 | 52/M | Right buttock (lung) | YAP1 exon 3 to KMT2A exon 5 | KMT2A exon 6 to YAP1 exon 5 | Not detected | Amplification of MDM2 and FRS2 | FoundationOne Heme® |
| 17 | 20/F | Thigh | YAP1 exon 5 to KMT2A exon 4 | KMT2A to YAP1 (exons not reported) | N/A | N/A | RNA-sequencing (Yoshida et al. case 1) |
| 18 | 45/F | Paraspinal | YAP1 exon 5 to KMT2A exon 4 | KMT2A exon 6 to YAP1 exon 9 | N/A | N/A | RNA-sequencing (Kao et al. case 1) |
| 19 | 45/F | Thigh | YAP1 exon 4 to KMT2A exon 5 | KMT2A exon 5 to YAP1 exon 9a | N/A | N/A | RNA-sequencing (Kao et al. case 2) |
| 20 | 47/M | Lower leg | YAP1 exon 5 to KMT2A exon 4 | KMT2A exon 6 to YAP1 exon 9 | N/A | N/A | RNA-sequencing (Kao et al. case 3) |
| 21 | 42/M | Thigh | YAP1 exon 5 to KMT2A exon 4 | Not detected | N/A | N/A | RT-PCR (Kao et al. case 8) |
| 22 | 22/M | Neck/paraspinal | Not detected | KMT2A exon 6 to YAP1 exon 9 | N/A | N/A | Targeted DNA NGS (Kao et al. case 9) |
| 23 | 91/F | Finger | YAP1 exon 6 to KMT2A exon 5b | KMT2A exon 6 to YAP1 exon 9 | N/A | N/A | RNA-sequencing (Puls et al. case 1) |
| 24 | 11/M | Supraclavicular fossa | YAP1 exon 5 to KMT2A exon 4 | KMT2A exon 6 to YAP1 exon 9 | N/A | N/A | RNA-sequencing (Puls et al. case 2) |
| 25 | 16/F | Heel/ankle | YAP1 exon 3 to KMT2A exon 5 | KMT2A exon 6 to YAP1 exon 8 | N/A | N/A | RNA-sequencing (Puls et al. case 3) |
| 26 | 53/M | Foot | YAP1 exon 5 to KMT2A exon 4 | KMT2A exon 6 to YAP1 exon 9 | N/A | N/A | RNA-sequencing (Puls et al. case 4) |
| 27 | 69/M | Chest wall | Not detected | KMT2A exon 6 to YAP1 exon 9 | N/A | N/A | RNA-sequencing (Puls et al. case 5) |
| 28 | 51/F | Thigh | YAP1 exon 4 to KMT2A exon 5 | KMT2A exon 6 to YAP1 exon 9 | N/A | N/A | RNA-sequencing (Puls et al. case 6) |
| 29 | 40/M | Thigh | YAP1 exon 4 to KMT2A exon 5 | KMT2A exon 6 to YAP1 exon 9 | N/A | N/A | RNA-sequencing (Puls et al. case 7) |
Data are presented using transcripts YAP1 NM_001130145 and KMT2A NM_001197104 (see “Methods”). Breakpoints in cases #1–16 are reported based on the highest read count.
aTranscript out-of-frame; breakpoints reported to be within exons.
bBreakpoint inside KMT2A exon 5 (AA 1143) involving the so-called “pre-CxxC” domain (1115–1154) that accounts for a portion of the multivalent bond with PAFc.