Table 1. PDX and Patient summaries.
All PDX and corresponding patient cancers had primary deleterious mutations in exon 11 of BRCA1 (now known as exon 10) as found by BROCA panel sequencing. Patient platinum response was classified as refractory (progression during treatment or within 4 weeks of last platinum dose), resistant (progression-free interval (PFI) < 6 months), partially-sensitive (PFI = 6–12 months), or sensitive (PFI > 12 months). PDX drug response classifications are outlined in Supplementary table 2. BRCA1 Δ11 and Δ11q isoform expression classification for PDX are described in Supplementary tables 3 and 4. HGSOC = high grade serous ovarian carcinoma; TNBC = triple negative breast cancer; OCS = ovarian carcinosarcoma; NR = information not relevant for TNBC; NA = data not available; TFI = treatment free interval; DOD = date of death; FU = follow up.
| Patient ID | Cancer type | BRCA1 mutations (transcript NM_007294.4) | Other mutations (BROCA panel) | Lines of therapy received for HGSOC | First platinu m TFI | Primary platinum status | Survival from diagnosis | D11q expression in PDX | D11 expression in PDX | PDX platinum response | PDX PARPi response | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Total for patient | Total prior to PDX | Platinum prior to PDX | PARPi prior to PDX? | |||||||||||
| #56 | HGSOC | Germline BRCA1 : c.895_896delGT | TP53: c.963del | 3 | 0 | 0 | No | 69 months | Sensitive | 96 months, DOD | Very Low | Very Low | Complete response | Partial Response |
| #56PP | HGSOC | Germline BRCA1 : c.895_896delGT and somatic BRCA1: c.670+281_1101 del (20%) | TP53 :c.963delA; PTEN: c.166delT | 8 | 5 | 2 | Yes | Low | Very high | Stable disease | Progressive disease | |||
| #206 | HGSOC | Germline BRCA1 : c.3817C>T | TP53 :c.451C>T; BLM rearrangement | 4 | 1 | 1 | No | 17 months | Sensitive | 39 months at last FU | Very Low | Very Low | Complete response | Complete response |
| #124 | TNBC | Germline BRCA1 : c.1961delA | TP53 : c.C844T; RAD51 : c.T659G | 4 | 4 | 1 | No | NR | NR | NA | Low | Very Low | Sensitive | Sensitive |
| #204 | TNBC | Germline BRCA1 : c.1105 1106insTC | TP53 : c.C451T; NBN: c.2006_2021 delinsA | NA | 0 | 0 | No | NR | NR | NA | Very Low | Very Low | Sensitive | Sensitive |
| #032 | HGSOC | Somatic BRCA1: c.1251delT | TP53 : c.97–1_97– 6del; FANCA : c.3788_3790del | 7 | 6 | 4 | Yes | 11 months | Partially Sensitive | 91 months, DOD | Moderate | Very Low | Stable disease | Progressive disease |
| #049 | HGSOC | Germline BRCA1 : c.2475delC and somatic BRCA1 : c.4096+3A>C (33%) | TP53 : c.428_429insCA | 7 | 4 | 3 | Yes | 5 months | Platinum resistant | 33 months at last FU | Very high | Very Low | Parital response | Stable disease |
| #196 | HGSOC | Germline BRCA1 : c.1961delA | TP53: c.G796A; ATM: c.G1595A | 5 | 5 | 3 | Yes | NA | NA | NA | Low | Very Low | Resistant | Resistant |
| #264 | OCS | Germline BRCA1 : c.2216_2217delAA | TP53 : c.1006G>T | 5 | 5 | 3 | Yes | 15 months | Sensitive | 9 3 mo nths, DOD | Very High | Very Low | Progressive disease | Progressive disease |