Article Figures & Data
Tables
- Table 1.
Spectrum of BRAF and NRAS mutations in invasive cutaneous melanomas (N = 214)
Gene Mutation Base change No. patients %* BRAF V600E GTG to GAG 60 28.0 V600K GTG to AAG 15 7.0 V600E GTG to GAA 4 1.9 V600R GTG to AGG 2 0.9 V600D GTG to GAT 1 0.5 VKS600-602DT† GTG-AAA-TCT to GAT-ACT 1 0.5 K601E AAA to GAA 2 0.9 K601N AAA to AAC 1 0.5 L597R CTA to CGA 1 0.5 D594N GAT to AAT 1 0.5 G469A GGA to GCA 1 0.5 G466E GGA to GAA 1 0.5 G455R GGG to AGG 1 0.5 G455E GGG to GAG 1 0.5 NRAS Q61K CAA to AAA 14 6.5 Q61R CAA to CGA 10 4.7 Q61L CAA to CTA 4 1.9 Q61H CAA to CAC 1 0.5 - Table 2.
Clinicopathologic characteristics by BRAF and NRAS mutational status among melanoma cases (N = 214)
Characteristic BRAF+ (n = 92) NRAS+ (n = 29) Wild-type (n = 93) BRAF+ vs wild-type, OR* (95% CI) NRAS+ vs wild-type, OR* (95% CI) Age at diagnosis (y) Mean ± SD, y 47.3 ± 14.1 62.1 ± 12.8 53.9 ± 17.9 P < 0.001† Per 10 y 0.8 (0.6-0.9) 1.3 (1.0-1.7) Gender, n (%) Male 48 (52) 17 (59) 52 (56) 1.0 1.0 Female 44 (48) 12 (41) 41 (44) 1.0 (0.5-1.8) 1.0 (0.4-2.5) Histologic subtype, n (%) SSM 79 (86) 23 (79) 67 (72) 1.0 1.0 NM 5 (5) 3 (10) 2 (2) 3.3 (0.6-18.2) 2.6 (0.4-17.9) LMM 5 (5) 2 (7) 15 (16) 0.4 (0.1-1.3) 0.2 (0.4-1.1) ALM/other‡ 3 (3) 1 (4) 9 (10) 0.3 (0.1-1.1) 0.3 (0.0-2.5) Breslow thickness (mm), n (%) <0.75 42 (46) 12 (41) 66 (71) 1.0 1.0 ≥0.75 50 (54) 17 (59) 27 (29) 3.2 (1.7-5.9) 3.2 (1.3-7.7) Abbreviations: BRAF+, BRAF-mutant; NRAS+, NRAS-mutant melanoma; Wild-type, melanoma negative for BRAF and NRAS mutations; SSM, superficial spreading melanoma; NM, nodular melanoma.
↵* OR values for gender, histologic subtype, and Breslow thickness are adjusted for age as a continuous variable.
↵† Two-sided ANOVA test for comparison of mean ages across BRAF+, NRAS+, and wild-type cases.
↵‡ This category includes two ALMs that were negative for BRAF and NRAS mutations and other melanomas that were nevoid, spitzoid, and unclassifiable.
- Table 3.
Phenotypic characteristics by BRAF and NRAS mutational status among melanoma cases (N = 214)
Characteristic BRAF+ (N = 92) NRAS+ (N = 29) Wild-type (N = 93) BRAF+ vs wild-type, OR* (95% CI) NRAS+ vs wild-type, OR* (95% CI) n† (%) No. nevi on the back Median (interquartile range) 14.5 (7-34) 12.0 (4-20) 9.0 (3-19) 0-4 14 (16) 9 (31) 32 (36) 1.0 1.0 5-14 31 (34) 9 (31) 28 (31) 2.4 (1.1-5.5) 1.2 (0.4-3.7) >14 45 (50) 11 (38) 29 (33) 3.2 (1.4-7.0) 1.7 (0.6-4.8) Ptrend 0.006 0.34 Nevus density diagrams None 11 (12) 5 (19) 27 (30) 1.0 1.0 Low 51 (58) 17 (62) 49 (55) 2.3 (1.0-5.2) 2.7 (0.8-8.6) Medium to high 26 (30) 5 (19) 13 (15) 3.8 (1.4-10.4) 3.3 (0.7-14.9) Ptrend 0.009 0.10 Propensity to tan Deep tan 20 (23) 5 (19) 11 (13) 1.0 1.0 Moderate tan 34 (38) 13 (48) 35 (41) 0.5 (0.2-1.3) 0.7 (0.2-2.6) Mild tan 27 (31) 6 (22) 24 (28) 0.7 (0.3-1.8) 0.4 (0.1-1.8) No tan 7 (8) 3 (11) 15 (18) 0.3 (0.1-0.9) 0.3 (0.1-1.6) Ptrend 0.13 0.09 Childhood freckles None 50 (56) 13 (45) 48 (52) 1.0 1.0 Few 31 (34) 14 (48) 29 (31) 0.9 (0.5-1.8) 2.0 (0.8-4.8) Many 9 (10) 2 (7) 16 (17) 0.5 (0.2-1.2) 0.5 (0.1-2.4) Ptrend 0.18 0.92 Hair color Black or dark brown 28 (30) 12 (41) 28 (30) 1.0 1.0 Light brown or blond 57 (62) 13 (45) 50 (54) 1.2 (0.6-2.3) 0.6 (0.2-1.4) Red 7 (8) 4 (14) 14 (15) 0.5 (0.2-1.5) 0.6 (0.2-2.4) Eye color Black or brown 26 (28) 7 (24) 26 (28) 1.0 1.0 Hazel, green, gray or blue 66 (72) 22 (76) 67 (72) 1.0 (0.5-2.0) 1.3 (0.5-3.4) - Table 4.
Indicators of sun exposure by BRAF and NRAS mutational status among melanoma cases (N = 214)
Characteristic BRAF+ (N = 92) NRAS+ (N = 29) Wild-type (N = 93) BRAF+ vs wild-type, OR* (95% CI) NRAS+ vs wild-type, OR* (95% CI) n† (%) Anatomic site Intermittently exposed site (trunk) 54 (59) 17 (59) 37 (40) 1.0 1.0 Chronically exposed sites (head/neck/extremities) 38 (41) 12 (41) 56 (60) 0.5 (0.3-1.0) 0.4 (0.2-0.9) CSD assessed by histologic solar elastosis Non-CSD 75 (82) 17 (59) 59 (63) 1.0 1.0 CSD 17 (18) 12 (41) 34 (37) 0.5 (0.3-1.2) 0.7 (0.3-1.9) Ambient erythemal UV irradiance, annual total in kJ/m2/y Lifetime (average of all decadal ages) Low UV (≤804) 17 (20) 9 (33) 30 (33) 1.0 1.0 High UV (>804) 70 (80) 18 (67) 60 (67) 2.0 (1.0-4.0) 1.1 (0.4-2.7) Early life (average of ages 0 and 10 y) Low UV (≤770) 14 (16) 11 (39) 30 (33) 1.0 1.0 High UV (>770) 75 (84) 17 (61) 60 (67) 2.6 (1.2-5.3) 0.9 (0.4-2.2) By decade‡ Birth year Low UV (≤751) 17 (19) 11 (39) 30 (33) 1.0 1.0 High UV (>751) 72 (81) 17 (61) 60 (67) 2.0 (1.0-4.1) 0.9 (0.4-2.2) Age 10 y Low UV (≤804) 17 (19) 12 (41) 29 (32) 1.0 1.0 High UV (>804) 73 (81) 17 (59) 61 (68) 1.9 (1.0-3.9) 0.8 (0.3-1.9) Age 20 y Low UV (≤783) 13 (14) 12 (41) 29 (33) 1.0 1.0 High UV (>783) 77 (86) 17 (59) 60 (67) 2.7 (1.3-5.7) 0.8 (0.3-1.9) Age 30 y Low UV (≤806) 25 (31) 14 (48) 30 (36) 1.0 1.0 High UV (>806) 57 (69) 15 (52) 53 (64) 1.0 (0.5-1.9) 0.7 (0.3-1.8) Age 40 y Low UV (≤806) 14 (22) 9 (31) 25 (34) 1.0 1.0 High UV (>806) 49 (78) 20 (69) 48 (66) 1.4 (0.6-3.3) 1.3 (0.5-3.4) Age 50 y Low UV (≤806) 8 (18) 5 (19) 20 (38) 1.0 1.0 High UV (>806) 37 (82) 21 (81) 32 (62) 1.2 (0.4-3.8) 2.5 (0.7-8.5) Age 60 y Low UV (≤807) 3 (17) 4 (25) 14 (38) 1.0 1.0 High UV (>807) 15 (83) 12 (75) 23 (62) 1.1 (0.2-7.0) 2.0 (0.4-9.8) - Table 5.
Relationship of age at diagnosis, number of back nevi, and estimated early-life ambient erythemal UV irradiance to BRAF and NRAS mutational status among melanoma cases (N = 202)
Characteristic BRAF+ vs wild-type, OR* (95% CI) NRAS+ vs wild-type, OR* (95% CI) Age at diagnosis (per 10 y) 0.8 (0.7-1.0) 1.4 (1.1-1.9) No. nevi on the back 0-4 1.0 1.0 5-14 2.8 (1.2-6.4) 1.1 (0.4-3.3) >14 3.4 (1.5-7.8) 1.9 (0.6-5.5) Ptrend 0.004 0.27 Early-life ambient UV irradiance in kJ/m2/y Low UV (≤770) 1.0 1.0 High UV (>770) 2.6 (1.2-5.6) 0.9 (0.4-2.2) NOTE: Subjects were 202 participants for whom no data were missing for the factors in the model.
↵* OR values are adjusted for all factors in the model.
Additional Files
Supplementary Data, Thomas et al
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Volume 16, Issue 5
