TABLE 1.
Breast cancer pathology, clinical features and NF1 mutations
| Breast cancer |
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|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age |
Pathology |
Mutations (DNA level; RNA level; Protein level) |
||||||||||||||
| ID | Diagnosis | Menarche | Type | ER | PR | HER2 | Ki-67 | Grade | Other neoplasms | NF1 features | Family history cancer | Family history NF1 | Female relative withbreast ca and NF1 | Exon | Type | Description |
| 1 | 56 | 13 | IDC | NA | NA | NA | NA | III | − | LN, AF, CN, PN | − | De novo | − | 33 [42] | OOF skipping exon 33 [42] - PSC | c.6364G>A; r.6085_6364del; p.Val2029Lysfs*7 |
| 2 | 53 | NA | IDC DICS | + | + | − | NA | III | Carcinoid tumor; Pheochromocytoma | SS, LN, CAL, AF, SC, CN, PN | Breast; Ovary; Esophagus | Inherited | − | 10c [14] | frameshift - PSC | c,1541_1542delAG; r,1541_1542delag; Gln514Argfs*43 |
| 3 | 60 | 16 | DCIS | 98% | 22% | NA | NA | NA | − | LD, MC, LN, CAL, AF, SC, CN, PN | Breast; Ovary; Pancreas; gastrium | De novo | − | 37 [46] | IF skipping exon 37 [46] | c.6792C>G; r.6757_6858del; p.Ala2253_Lys2286del |
| 4 | 49 | NA | IDC DCIS | − | − | + | NA | II | Cervical cancer | LN, CAL, CN | Breast; Pheochromocytoma | Inherited | NA | 15 [20] | nonsense - PSC | c.2398G>T, r.2398g>u; p.Glu800* |
| 5 | 45 | 14 | NA | NA | NA | NA | NA | NA | − | SS, CAL, AF, CN | − | De novo | − | Intron 26 [34] | OOF splicing - PSC | c.4515-20_4515-18delAAG; r.4514_4515ins4515-14_4515-1; p.Argl505Serfs*53 |
| 6 | 47 | 11 | IDC DCIS LCIS | >90% | 70% | − | NA | II | − | SS, LN, CAL, AF, CN | Breast; Prostate | NA | − | 16 [21] | Truncation and low level OOF splicing - PSC | c.2621_2634dupAGGGTTCTATGATT; r.2621_2634dupaggguucuaugauu and r.2618_2850del; p.Ser879Argfs*4 and p.Lys874Phefs*4 |
| 7 | 39 | NA | IDC DCIS | 82% | 71% | NA | NA | III | − | SS, LN, CAL, AF, NF, PN | − | Inherited | − | 29–30 [38–39] | copy number variant - PSC | c.(5045_5337}_(5625_5796}del; r.5206_5749del; p.Glyl737Leufs*3 |
| 8 | 41 | 11 | IDC DCIS | + | − | Eq | NA | II | − | SS, CAL, AF, PN | Lung; Colon; Pheochromocytoma | Inherited | − | 12a [16] | Mis-sense | C.1733T>G; r,1733u>g; p.Leu578Arg |
| 9 | 49 | 14 | IDC DCIS | 30% | − | + | 20% | II | − | LN, CAL, AF | Breast | NA | NA | Intron 31 [40]) | OOF splicing - PSC | c.5943 + 1G>T; leads to out-of-frame splice r.5901_5943del; p.Met1967llefs*10 |
| 10 | 44 | NA | IDC DCIS | 80% | 100% | − | 15% | II | − | CAL, AF, SC, CN | Breast; Colon; Lung; Prostate | Inherited | NA | 16 [21] | frameshift - PSC | c.2728_2729delGG; r.2728_2729delgg; p.Gly910Thrfs*8 |
| 11 | 58 | NA | NA | NA | NA | NA | NA | NA | − | CAL, AF, BD, CN, PN | − | NA | NA | 28 [37] | frameshift - PSC | c.4910_4911delTT; r.4910_4911deluu; p.Phel637Serfs*3 |
| 12 | 52 | 13 | IDC | − | − | + | NA | III | − | LD, LN, AF, CN | Breast; Gastrium | De novo | − | 30 [39] | frameshift - PSC | c.5667dupT; r.5667dupu; p.llel890Tyrfs*2 |
| 13 | 47 | 13 | IDC DCIS | 24% | 2% | − | 59% | III | − | SS, MC, AF, CN | Breast; Ovary | Inherited | + | 9 [11] | deep intronic splice mutation - PSC | c.1260 + 1604A>G, r,1260_1261ins1260 + 1605_1260 +1646; p.Ser421_Val2818delinsLeuThrThr* |
| 14 | 42 | 13 | IDC DCIS | + | + | − | 10% | II | − | SS, CAL, AF, CN | Breast; Ovary | Inherited | + | 9 [11] | deep intronic splice mutation - PSC | c.1260+1604A>G, r,1260_1261ins1260 + 1605_1260 +1646; p.Ser421_Val2818delinsLeuThrThr* |
Abbreviations: IDC, invasive ductal carcinoma; DCIS, ductal carcinoma in situ; NA, information not available; ER, estrogen receptor status; PR, progesterone receptor status; HER2, human epidermal growth factor receptor 2 expression; Ki-67, Ki-67 proliferation marker; Eq, equivocal. Grade: I = Well differentiated, II = Moderately differentiated, III = Poorly differentiated. NF1 Features, that is physical features: SS (short stature); LD (learning disability); MC (macrocephaly); LN (Lisch nodules); CAL (>= 6 café au lait macules); AF (axillary freckling); BD (bony dysplasia); SC (scoliosis); CN (>= cutaneous neurofibromas); PN (plexiform neurofibroma). OOF, Out-of-frame; IF: In-frame; PSC: premature stop-codon.