ABCMdb

ABCB11 p.Ala389Pro

Predicted by SNAP2:	C: N (61%), D: D (80%), E: D (80%), F: D (80%), G: D (53%), H: D (59%), I: D (71%), K: D (80%), L: D (75%), M: D (66%), N: D (71%), P: D (85%), Q: D (71%), R: D (75%), S: N (72%), T: D (63%), V: D (66%), W: D (85%), Y: D (80%),
Predicted by PROVEAN:	C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: N, T: D, V: D, W: D, Y: D,

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Publications
[hide] Paediatric hepatocellular carcinoma due to somatic... J Hepatol. 2014 Nov;61(5):1178-83. doi: 10.1016/j.jhep.2014.07.003. Epub 2014 Jul 10. Vilarinho S, Erson-Omay EZ, Harmanci AS, Morotti R, Carrion-Grant G, Baranoski J, Knisely AS, Ekong U, Emre S, Yasuno K, Bilguvar K, Gunel M
Paediatric hepatocellular carcinoma due to somatic CTNNB1 and NFE2L2 mutations in the setting of inherited bi-allelic ABCB11 mutations.
J Hepatol. 2014 Nov;61(5):1178-83. doi: 10.1016/j.jhep.2014.07.003. Epub 2014 Jul 10., [PMID:25016225]

Abstract [show]
Hepatocellular carcinoma (HCC) rarely occurs in childhood. We describe a patient with new onset of pruritus at 8 months of age who at 17 months of age was found to have a 2.5 cm HCC. To delineate the possible genetic basis of this tumour, we performed whole exome sequencing (WES) of the germline DNA and identified two novel predictably deleterious missense mutations in ABCB11, encoding bile salt export pump (BSEP), confirmed in the parental DNA as bi-allelic and inherited. Although inherited ABCB11 mutations have previously been linked to HCC in a small number of cases, the molecular mechanisms of hepatocellular carcinogenesis in ABCB11 disease are unknown. WES of the HCC tissue uncovered somatic driver mutations in the beta-catenin (CTNNB1) and nuclear-factor-erythroid-2-related-factor-2 (NFE2L2) genes. Moreover, clonality analysis predicted that the CTNNB1 mutation was clonal and occurred earlier during carcinogenesis, whereas the NFE2L2 mutation was acquired later. Interestingly, background liver parenchyma showed no inflammation or fibrosis and BSEP expression was preserved. This is the first study to identify somatic CTNNB1 and NFE2L2 mutations in early childhood arisen in the setting of inherited bi-allelic ABCB11 mutations. Rapid WES analysis expedited this child's diagnosis and treatment, and likely improved her prognosis.

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No. Sentence Comment
105 One study showed that 7% 395 395 395 395 395 397 393 FATGRAAATSIFE FATGRAAATSIFE FATGRAAATSIFH FAAGRAAAASIFE FSTGCSAASSIFQ FATGRGAAANIFE FAAGRGAATIIFE Human Chimpanzee Dog Cow Mouse Chicken Zebrafish BSEP A389P SRGEKQRIAIARA SRGEKQRIAIARA SRGEKQRIAIARA SRGEKQRIAIARA SRGEKQRIAIARA SRGQKQRIAIARA SRGQKQRIAIARA Human Chimpanzee Dog Cow Mouse Chicken Zebrafish 1232 1232 1236 1235 1232 1245 1242 BSEP R1226H A C D E B Fig. 1. Login to comment
107 Compound heterozygous missense mutations in ABCB11: R1226H and A389P, and their conservation across species (A and B respectively). Login to comment