Table 1.
Mutations detected in cultured CTC lines.
| Case | Gene | DNA | Protein | Allele frequency† | In pretreatment tumor‡ | In multiple CTC lines | Known mutation§ |
|---|---|---|---|---|---|---|---|
| BRx33‖ | ESR1 | A1613G | D538G | 0.24 | – | – | Br,# En |
| NUMA1 | C5501T | S1834L | 0.39 | – | – | Br | |
| BRx07‖ | TP53 | G853A | E285K | 0.99 | No | – | Bl, Br, Co, HN, Lu |
| PIK3CA | A3140T | H1047L | 1 | No | – | Br, Co, GBM, HN, Ki, Lu, Me, Mel, Ov, En | |
| FGFR2 | T1647A | N549K | 0.46 | No | – | Br, En | |
| CDH1 | C790T | Q264* | 1 | Yes | – | Br | |
| APC | G7225A | G2409R | 0.47 | Yes | – | Mel | |
| DGKQ | G2530A | D844N | 0.55 | – | – | Lu | |
| MAML2 | A2569G | M857V | 0.52 | – | – | Lu | |
| BRx68 | TP53 | C1009T | R337C | 0.99 | No | Yes | Br, Co, HN, Hem, Ov |
| ESR1 | A1610C | Y537S | 0.47 | No | Yes | Br#, En | |
| PIK3CA | A3140G | H1047R | 0.7 | Yes | Yes | Br, Co, GBM, HN, Ki, Lu, Me, Mel, Ov, En | |
| MSN | G1153A | E385K | 0.25 | – | – | En | |
| BRx50‖ | ESR1 | T1607C | L536P | 0.06†† | – | – | Br# |
| IKZF1 | G1444T | G482C | 0.09 | – | – | Hem | |
| BRCA2¶ | T6262del | L2039fs | – | – | – | Br (germ line) | |
| BRx42 | PIK3CA | G3145C | G1049R | 0.60 | Yes | Yes | Br, En, Ki |
| PIK3CA | C1097G | P366R | 0.54 | – | – | Br | |
| KRAS | G35T | G12V | 0.99 | No | Yes | Br, Co, Hem, Es, GBM, Lu, Ov, En | |
| IGF1R | G3613A | A1205T | 0.06 | – | – | Hem | |
| BRx61 | TP53 | G610T | E204* | 0.98 | No | Yes | Bl, Br, Ki, Lu, Ov |
Mutant allele frequency within oligoclonal cultured CTC populations was calculated as the ratio of mutant sequence reads to total reads for each gene.
Where sufficient material was available for analysis, matched archival pretreatment tumor specimens were subjected to Sanger sequencing to confirm selected mutations identified in CTC cultures. Insufficient tumor material is marked (–).
List of tumor types reported to harbor the same mutation in pan-cancer (10) or COSMIC databases. Abbreviations: breast (Br), endometrial (En), central nervous system (CNS), bladder (Bl), colorectal (Co), pancreas (Pa), stomach (St), head and neck (HN), lung (Lu), thyroid (Th), glioblastoma (GBM), kidney (Ki), prostate (Pr), medulloblastoma (Me), melanoma (Mel), ovarian (Ov), cervix (Ce), esophageal (Es), hematopoietic and lymphoid tissue (Hem), sarcoma (Sar), cholangiocarcinoma (Ch).
Cases for which DNA from matched normal tissue was not available.
Germline BRCA2 mutation was detected as part of genetic counseling for familial breast cancer. #Mutations reported in recent publications (12–15). ††ESR1 T1607C mutant allele frequency increased to 0.49 after prolonged in vitro culture under low-estrogen conditions (>6 months).
Chain termination codon. fs: frameshift mutation. Abbreviations for amino acid residues: A, Ala; C, Cys; D, Asp; E, Glu; F, Phe; G, Gly; H, His; I, Ile; K, Lys; L, Leu; M, Met; N, Asn; P, Pro; Q, Gln; R, Arg; S, Ser; T, Thr; V, Val; W, Trp; and Y, Tyr.