This work is licensed under a Table 2.
Summary of clinical and experimental data in studied subjects from 15 families with small intestine neuroendocrine tumors (SI-NETs).
| TERT Variants | Variants in SDH genes | Variants in excision-repair genes | Experiments performed | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Family no./ID | Subject ID | Gender | Affected (Yes/No) | Age at diagnosis | Survival (years)a | WHOb | Tumor stagec | TERT | SDHA | SDHB | SDHD | MUTYH | OGG1 | NGS of blood DNAd | NGS of tumor DNAd | Illumina SNP array on blood DNAe | Illumina SNP array on tumor DNAe |
| 1/A | A1 | F | Y | 45 | 27.3 (AWD) | 1 | TxN1M1 | p.(Ala279Thr) | WGS (35×) WES (78×) | WES (25×) | 610Q 2.5 M Omni | 610Q (PT) | |||||
| A2 | M | Y | 34 | 13.5 (AWD) | 1 | TxN1M1 | p.(Ala279Thr) p.(His412Tyr) | WGS (35×) WES (89×) | – | 2.5 M Omni | – | ||||||
| A3 | M | N | – | – | – | – | p.(Ala279Thr) | – | – | 2.5 M Omni | – | ||||||
| A4 | M | N | – | – | – | – | p.(His412Tyr) | WES (146×) | – | 2.5 M Omni | – | ||||||
| A5 | M | N | – | – | – | – | – | – | 2.5 M Omni | – | |||||||
| A6 | F | Y | 35 | n.a. | n.a. | n.a. | p.(Ala279Thr) | p.(Gly12Ser) | WES (164×) | – | 2.5 M Omni | – | |||||
| A7 | M | Y | 42 | 6.2 (AWD) | 2 | TxN1M1 | p.(Ala279Thr) | WGS (33×) WES (87×) | – | 2.5 M Omni | – | ||||||
| 2/B | B1 | F | N | – | – | – | – | – | – | 2.5 M Omni | |||||||
| B2 | M | Y | 62 | 15+ | n.a. | TxN1M1 | – | – | – | 610Q (M) | |||||||
| B3 | M | Y | 42 | 5.8+ | 2 | TxN1M1 | p.(Ala279Thr) | WES (89×) | WES (27×) | 610Q 2.5 M Omni | 2.5 M Omni (PT) | ||||||
| 3/C | C2 | F | Y | 68 | 5.2+ | 2 | TxN1M1 | WES (78×) | – | – | – | ||||||
| 4/D | D8 | F | Y | 63 | 4.3+ | n.a. | TxN1M1 | p.(His50Arg) | WGS (32×) | – | 610Q 2.5 M Omni | – | |||||
| D9 | F | Y | 59 | 11.7+ | 1 | TxN1M1 | p.(His50Arg) | WGS (27×) | – | 610Q 2.5 M Omni | – | ||||||
| 5/E | E10 | F | Y | 62 | 6.3+ | n.a. | TxN1M0 | WES (111×) | – | 2.5 M Omni | – | ||||||
| E11 | M | Y | 67 | 19.4+ | n.a. | TxN1M0 | WES (129×) | – | 2.5 M Omni | – | |||||||
| E12 | F | Y | 62 | 5.4+ | 1 | TxN1M1 | WES (188×) | – | 2.5 M Omni | – | |||||||
| 6/F | F1 | M | Y | 38 | 29+ | n.a. | TxN1M1 | – | – | – | |||||||
| F2 | F | Y | 66 | 6.3 (AWD) | 1 | TxN1M1 | WES (89×) | WES (28×) | 610Q 2.5 M Omni | 610Q (M) 610Q (PT) 2.5 M Omni (PT) | |||||||
| 7/G | G1 | F | Y | 68 | 6.4+ | 1 | TxN1M1 | p.(Asp38Val) | WGS (33×) WES (87×) | – | 610Q 2.5 M Omni | 610Q (M) | |||||
| G2 | F | Y | 50 | n.a. | n.a. | TxN1M0 | p.(Asp38Val) | WGS (34×) | – | 610Q 2.5 M Omni | 610Q (M) | ||||||
| 8/H | H2 | M | Y | 52 | 8+ | 1 | TxN1M1 | WES (81×) | WES (35×) | 610Q 2.5 M Omni | 610Q (M) | ||||||
| 9/J | J1 | F | Y | 40 | 12 (AWD) | 1 | TxN1M1 | WES (139×) | – | 2.5 M Omni | – | ||||||
| 10/K | K1 | M | Y | 60 | 6.9 (AWD) | 2 | TxN1M1 | WES (200×) | – | 2.5 M Omni | – | ||||||
| 11/M | M1 | M | Y | 66 | 8.8+ | 2 | TxN1M1 | p.(Arg46Gln) | WES (74×) | – | 2.5 M Omni | – | |||||
| M2 | M | Y | 43 | 4 (AWD) | 2 | TxN1M1 | p.(Ala279Thr) | p.(Ser163Pro) | WES (88×) | – | 2.5 M Omni | – | |||||
| M3 | M | N | – | – | – | – | p.(Ala279Thr) | p.(Ser163Pro) | p.(Arg46Gln) | WES (91×) | – | – | – | ||||
| M4 | F | N | – | – | – | – | WES (88×) | – | – | – | |||||||
| 12/N | N1 | M | Y | 63 | 2.8 (AWD) | 1 | TxN1M0 | WES (91×) | – | ||||||||
| N2 | F | N | – | – | – | – | WES (77×) | – | |||||||||
| 13/No | No1 | F | Y | 57 | 10.8 (AWD) | 1 | T3N2M1 | p.(Gly396Asp) | WES (86×) | – | – | – | |||||
| No2 | M | Y | 49 | 3.8 (AWD) | 2 | T3N0M1 | WES (78×) | – | – | – | |||||||
| 14/O | O1 | F | Y | 57 | 3.4 (AWD) | 2 | TxN1M0 | p.(Gly396Asp) | WES (80×) | – | 2.5 M Omni | ||||||
| 15/P | P1 | M | Y | 39 | 20+ | n.a. | TxN1M1 | WES (82×) | – | – | – | ||||||
AWD, alive with disease; +deceased; bgrade of tumor according to Rindi G, Arnold R, Bosman FT. Nomenclature and classification of neuroendocrine neoplasms of the digestive system. In: Bosman FT, Carneiro F, Hruban RH, Theise ND et al., editors. WHO classification of tumors of the digestive system. Lyon: IARC, 2010; ctumors classified according to: Rindi G, Kloppel G, Alhman H, Caplin M, Couvelard A et al. TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system. Virchows Arch 2006, 449:395–401; dabbreviations: WGS, whole-genome sequencing. WES, whole-exome sequencing. The number in parentheses denotes the read depth of the NGS experiments. The coverage was calculated for WES data by using the software GATK (DeptOfCoverage) on exome target regions, while for whole-genome experiments the overall coverage was calculated by extracting the total base coverage from BAM alignments with Samtools (depth) and then dividing this number by the human genome size (3.1 billion bases); eDNA extracted from blood and tumors (in parenthesis: PT-primary tumor; M-metastasis) was genotyped on two platforms: Illumina Human610-Quad BeadChip (610Q) and Illumina Omni 2.5 BeadChip (2.5 M Omni).
n.a., data not available.