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10

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19 © 2009 NHS National Genetics Education and Development Centre Genetics and Genomics for Healthcarewww.geneticseducation.nhs.uk

Fig. 13.3 ©Scion Publishing Ltd

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Hereditary Breast and Ovarian Cancer : HBOC

31

•2013 5 17

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•Cannon-Albright L A et al. Important Advances in Oncology. J. B. Lippencott Publishers, Philadelphia, 39-55, 1991

8 %1/12

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33

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p53

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Hereditary Breast and Ovarian Cancer : HBOC

BRCA1 25-30% BRCA2 25-30% 50-60%

34

35

Myriad myRisk™25

BR = BreastOV = OvarianCO = ColorectalEN = EndometrialME = MelanomaPA = PancreaticGA = GastricPR = ProstateOC = Other Cancers / Clinical Features

MYRIAD myRiskTM Clinical Handbook 35

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37

RESEARCH ARTICLESA Strong Candidate for the Breast and Ovarian Cancer SusceptibilityGene BRCA1Yoshio Miki, Jeff Swensen, Donna Shattuck Eidens, et al.

Science. 1994 Oct 7;266(5182):66 71.

AbstractA strong candidate for the 17q linked BRCA1 gene, which influences susceptibility to breastand ovarian cancer, has been identified by positional cloning methods. Probable predisposingmutations have been detected in five of eight kindreds presumed to segregate BRCA1susceptibility alleles. The mutations include an 11 base pair deletion, a 1 base pair insertion,a stop codon, a missense substitution, and an inferred regulatory mutation. The BRCA1 geneis expressed in numerous tissues, including breast and ovary, and encodes a predicted proteinof 1863 amino acids. This protein contains a zinc finger domain in its amino terminal region,but is otherwise unrelated to previously described proteins. Identification of BRCA1 shouldfacilitate early diagnosis of breast and ovarian cancer susceptibility in some individuals aswell as a better understanding of breast cancer biology.

38

d.56y d.61y

BRCA1+

BRCA1(+)

BRCA1 ?

39

BRCA1/2

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(variant of uncertainsignificance : VUS)

VUS41

BRCA1/2

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42

BRCA1/2

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45

[ ]A: Meijers-Heijboer H et al. The New England Journal of Medicine 345(3):159-164, 2001B: Rebbeck TR et al. Journal of Clinical Oncology 22(6):1055-1062, 2004

(case) (control)

76 0 63 8 - A

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46

[ ] Finch A et al. JAMA 296(2):185-192, 2006

BRCA1/2-

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47

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5.

49 50

1. BRCA

BRCAPARP

BRCA

2.DNA

PD1 PD-L1

51

BRCA1/2

DNA

PARP

PARP BRCA1/2 synthetic lethal therapy

BRCA1/2PARP

DNA

52

PD 1 Blockade in Tumors with Mismatch Repair DeficiencyDung T. Le, et al. N Engl J Med Volume 372(26):2509 2520 June 25, 2015

DNA

DNA

DNA

53

HBOC http://hboc.jp/index.html

54

•

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55

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( )

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••• HBOC

MRI

1

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57miki.mgen@mri.tmd.ac.jp

58