ABCMdb

PMID: 12011154

Potocnik U, Ravnik-Glavac M, Golouh R, Glavac D
Naturally occurring mutations and functional polymorphisms in multidrug resistance 1 gene: correlation with microsatellite instability and lymphoid infiltration in colorectal cancers.
J Med Genet. 2002 May;39(5):340-6., [PubMed]

Sentences

No. Mutations Sentence Comment

214 ABCB1 p.Gly1265Ser (A) Germline mutation in exon 28 of the MDR1 gene identified in tumour sample MSI 11. Arrow indicates G>A substitution at position 3793 resulting in an amino acid change at position 1265 from non-polar glycine to polar serine (G1265S). Login to comment 240 ABCB1 p.Gly1265Ser The germline G1265S substitution identified in sample MSI 11 was of special interest (fig 2). Login to comment 242 ABCB1 p.Gly1265Ser ABCB1 p.Gly1265Ser G1265S was also the only germline alteration that resulted in substitution of an amino acid conserved through species; in this case non-polar Gly is replaced by polar Ser. The G1265S substitution is located in the predicted IC12 domain after the ATP binding site. Login to comment 247 ABCB1 p.Gly1265Ser ABCB1 p.Ile1050Thr ABCB1 p.Leu70Pro Table 1 Mutations and germline promoter functional polymorphism in the MDR1 gene identified in colorectal cancers with microsatellite instability Sample Origin Exon Nucleotide change Consequence Amino acid change Domain Consensus MSI 3 Germline Promoter +8 T>C* Somatic 25 3149 T>C I1050T Non-polar>polar IC6 Yes MSI 5 Germline Promoter +8 T>C* Somatic 4 209 T>C L70P Non-polar>non-polar TM1 Yes MSI 11 Somatic Promoter -14 G>T Germline 28 3793 G>A G1265S Non-polar>polar IC6 Yes MSI 19 Somatic Promoter -29 G>A Somatic 20 2422-2426 del A Frameshift IC4 MSI 22 Germline Promoter +8 T>C* MSI 34 Germline 8 729 A>G E243 no change / / / IC=intracelular domain, TM=transmembrane domain. Login to comment 264 ABCB1 p.Ser400Asn ABCB1 p.Asn21Asp To the best of our knowledge, this Table 2 Correlation between MDR1 polymorphisms and increased lymphoid infiltration in tumours Exon Genotype (polymorphism) Amino acid change No (%) of tumours with specific genotype (polymorphism)/No of tumours analysed No (%) of tumours with specific genotype (polymorphism) and lymphoid infiltration p* Promoter †Promoter +8 T/T 313/327 (96%) 152/313 (49%) Promoter Promoter +8 T/C Non-coding 14/327 (4%) 9/14 (64%) 0.036 Intron 1b IVS1-81 (G)4 311/327 (95%) 149/311 (48%) Intron 1b IVS1-81 (G)4/(G)3 Non-coding 16/327 (5%) 12/16 (75%) 0.010 Intron 1b ‡IVS-1 G/G 271/317 (85%) 127/271 (47%) Intron 1b IVS-1 G/A 45/317 (14%) 27/45(60%) NS Intron 1b IVS-1 A/A Non-coding 1/317 (<1%) 1/1 (100%) NS 2 ‡61 A/A 266/321 (83%) 125/266 (47%) 2 61 A/G Asn21Asp 51/321 (16%) 29/51 (57%) NS 2 61 G/G 4/321 (1%) 2/4 (50%) NS Intron 4 ‡IVS4-25 G/G 44/63 (70%) 19/44 (43%) Intron 4 IVS4-25 G/T Non-coding 15/63 (24%) 7/15 (47%) NS Intron 4 IVS4-25 T/T 4/63 (6%) 2/4 (50%) NS 11 1199 G/G 307/327 (94%) 152/307 (50%) 11 1199 G/A Ser400Asn 20/327 (6%) 11/20 (55%) NS 12 ‡1236 C/C 81/327 (25%) 39/81 (48%) 12 1236 C/T No change 163/327 (50%) 80/163 (49%) NS 12 1236 T/T 83/327 (25%) 42/83 (51%) NS Intron 16 IVS16+158 G/G 82/87 (94%) 41/82 (50%) Intron 16 IVS16+158 G/A Non-coding 5/87 (6%) 3/5 (60%) NS 21 §2677 G/G 14/41 (34%) 7/14 (50%) 21 2677 G/T Ala893Ser 17/41 (41%) 7/17 (41%) NS 21 2677 T/T 10/41 (24%) 4 /10 (40%) NS 26 ‡3435 C/C 44/159 (28%) 18/44 (41%) 26 3435 C/T No change 85/159 (53%) 46/85 (54%) NS 26 3435 T/T 30/159 (19%) 15/30 (50%) NS NS=not significant. Login to comment