Haplotype and phenotype analysis of nine recurrent BRCA2 mutations in 111 families: results of an international study

S L Neuhausen; A K Godwin; R Gershoni-Baruch; E Schubert; J Garber; D Stoppa-Lyonnet; E Olah; B Csokay; O Serova; F Lalloo; A Osorio; M Stratton; K Offit; J Boyd; M A Caligo; R J Scott; Andrew Craig Schofield; E Teugels; M Schwab; L Cannon-Albright; T Bishop; D Easton; J Benitez; M C King; B A Ponder; B Weber; P Devilee; A Borg; S A Narod; D Goldgar

doi:10.1086/301885

Haplotype and phenotype analysis of nine recurrent BRCA2 mutations in 111 families: results of an international study

S L Neuhausen, A K Godwin, R Gershoni-Baruch, E Schubert, J Garber, D Stoppa-Lyonnet, E Olah, B Csokay, O Serova, F Lalloo, A Osorio, M Stratton, K Offit, J Boyd, M A Caligo, R J Scott, Andrew Craig Schofield, E Teugels, M Schwab, L Cannon-AlbrightT Bishop, D Easton, J Benitez, M C King, B A Ponder, B Weber, P Devilee, A Borg, S A Narod, D Goldgar

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Abstract

Several BRCA2 mutations are found to occur in geographically diverse breast and ovarian cancer families. To investigate both mutation origin and mutation-specific phenotypes due to BRCA2, we constructed a haplotype of 10 polymorphic short tandem-repeat (STR) markers flanking the BRCA2 locus, in a set of 111 breast or breast/ovarian cancer families selected for having one of nine recurrent BRCA2 mutations. Six of the individual mutations are estimated to have arisen 400-2,000 years ago. In particular, the 6174delT mutation, found in approximately 1% of individuals of Ashkenazi Jewish ancestry, was estimated to have arisen 29 generations ago (1-LOD support interval 22-38). This is substantially more recent than the estimated age of the BRCA1 185delAG mutation (46 generations), derived from our analogous study of BRCA1 mutations. In general, there was no evidence of multiple origins of identical BRCA2 mutations. Our study data were consistent with the previous report of a higher incidence of ovarian cancer in families with mutations in a 3.3-kb region of exon 11 (the ovarian cancer cluster region [OCCR]) (P=.10); but that higher incidence was not statistically significant. There was significant evidence that age at diagnosis of breast cancer varied by mutation (P

Original language	English
Pages (from-to)	1381-1388
Number of pages	8
Journal	American Journal of Human Genetics
Volume	62
Issue number	6
DOIs	https://doi.org/10.1086/301885
Publication status	Published - 1 Jun 1998

Keywords

Adult
BRCA2 Protein
Breast Neoplasms
Breast Neoplasms, Male
Evolution, Molecular
Female
Genetic Markers
Genotype
Haplotypes
Humans
Male
Mutation
Neoplasm Proteins
Ovarian Neoplasms
Phenotype
Polymorphism, Genetic
Repetitive Sequences, Nucleic Acid
Transcription Factors
BRCA2
Breast cancer
Ovarian cancer
Mutation origin
Cancer, breast
Cancer, Ovarian

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1086/301885

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Neuhausen, S. L., Godwin, A. K., Gershoni-Baruch, R., Schubert, E., Garber, J., Stoppa-Lyonnet, D., Olah, E., Csokay, B., Serova, O., Lalloo, F., Osorio, A., Stratton, M., Offit, K., Boyd, J., Caligo, M. A., Scott, R. J., Schofield, A. C., Teugels, E., Schwab, M., ... Goldgar, D. (1998). Haplotype and phenotype analysis of nine recurrent BRCA2 mutations in 111 families: results of an international study. American Journal of Human Genetics, 62(6), 1381-1388. https://doi.org/10.1086/301885

Neuhausen, SL, Godwin, AK, Gershoni-Baruch, R, Schubert, E, Garber, J, Stoppa-Lyonnet, D, Olah, E, Csokay, B, Serova, O, Lalloo, F, Osorio, A, Stratton, M, Offit, K, Boyd, J, Caligo, MA, Scott, RJ, Schofield, AC, Teugels, E, Schwab, M, Cannon-Albright, L, Bishop, T, Easton, D, Benitez, J, King, MC, Ponder, BA, Weber, B, Devilee, P, Borg, A, Narod, SA & Goldgar, D 1998, 'Haplotype and phenotype analysis of nine recurrent BRCA2 mutations in 111 families: results of an international study', American Journal of Human Genetics, vol. 62, no. 6, pp. 1381-1388. https://doi.org/10.1086/301885

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abstract = "Several BRCA2 mutations are found to occur in geographically diverse breast and ovarian cancer families. To investigate both mutation origin and mutation-specific phenotypes due to BRCA2, we constructed a haplotype of 10 polymorphic short tandem-repeat (STR) markers flanking the BRCA2 locus, in a set of 111 breast or breast/ovarian cancer families selected for having one of nine recurrent BRCA2 mutations. Six of the individual mutations are estimated to have arisen 400-2,000 years ago. In particular, the 6174delT mutation, found in approximately 1% of individuals of Ashkenazi Jewish ancestry, was estimated to have arisen 29 generations ago (1-LOD support interval 22-38). This is substantially more recent than the estimated age of the BRCA1 185delAG mutation (46 generations), derived from our analogous study of BRCA1 mutations. In general, there was no evidence of multiple origins of identical BRCA2 mutations. Our study data were consistent with the previous report of a higher incidence of ovarian cancer in families with mutations in a 3.3-kb region of exon 11 (the ovarian cancer cluster region [OCCR]) (P=.10); but that higher incidence was not statistically significant. There was significant evidence that age at diagnosis of breast cancer varied by mutation (P",

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author = "Neuhausen, {S L} and Godwin, {A K} and R Gershoni-Baruch and E Schubert and J Garber and D Stoppa-Lyonnet and E Olah and B Csokay and O Serova and F Lalloo and A Osorio and M Stratton and K Offit and J Boyd and Caligo, {M A} and Scott, {R J} and Schofield, {Andrew Craig} and E Teugels and M Schwab and L Cannon-Albright and T Bishop and D Easton and J Benitez and King, {M C} and Ponder, {B A} and B Weber and P Devilee and A Borg and Narod, {S A} and D Goldgar",

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T1 - Haplotype and phenotype analysis of nine recurrent BRCA2 mutations in 111 families: results of an international study

AU - Neuhausen, S L

AU - Godwin, A K

AU - Gershoni-Baruch, R

AU - Schubert, E

AU - Garber, J

AU - Stoppa-Lyonnet, D

AU - Olah, E

AU - Csokay, B

AU - Serova, O

AU - Lalloo, F

AU - Osorio, A

AU - Stratton, M

AU - Offit, K

AU - Boyd, J

AU - Caligo, M A

AU - Scott, R J

AU - Schofield, Andrew Craig

AU - Teugels, E

AU - Schwab, M

AU - Cannon-Albright, L

AU - Bishop, T

AU - Easton, D

AU - Benitez, J

AU - King, M C

AU - Ponder, B A

AU - Weber, B

AU - Devilee, P

AU - Borg, A

AU - Narod, S A

AU - Goldgar, D

PY - 1998/6/1

Y1 - 1998/6/1

N2 - Several BRCA2 mutations are found to occur in geographically diverse breast and ovarian cancer families. To investigate both mutation origin and mutation-specific phenotypes due to BRCA2, we constructed a haplotype of 10 polymorphic short tandem-repeat (STR) markers flanking the BRCA2 locus, in a set of 111 breast or breast/ovarian cancer families selected for having one of nine recurrent BRCA2 mutations. Six of the individual mutations are estimated to have arisen 400-2,000 years ago. In particular, the 6174delT mutation, found in approximately 1% of individuals of Ashkenazi Jewish ancestry, was estimated to have arisen 29 generations ago (1-LOD support interval 22-38). This is substantially more recent than the estimated age of the BRCA1 185delAG mutation (46 generations), derived from our analogous study of BRCA1 mutations. In general, there was no evidence of multiple origins of identical BRCA2 mutations. Our study data were consistent with the previous report of a higher incidence of ovarian cancer in families with mutations in a 3.3-kb region of exon 11 (the ovarian cancer cluster region [OCCR]) (P=.10); but that higher incidence was not statistically significant. There was significant evidence that age at diagnosis of breast cancer varied by mutation (P

AB - Several BRCA2 mutations are found to occur in geographically diverse breast and ovarian cancer families. To investigate both mutation origin and mutation-specific phenotypes due to BRCA2, we constructed a haplotype of 10 polymorphic short tandem-repeat (STR) markers flanking the BRCA2 locus, in a set of 111 breast or breast/ovarian cancer families selected for having one of nine recurrent BRCA2 mutations. Six of the individual mutations are estimated to have arisen 400-2,000 years ago. In particular, the 6174delT mutation, found in approximately 1% of individuals of Ashkenazi Jewish ancestry, was estimated to have arisen 29 generations ago (1-LOD support interval 22-38). This is substantially more recent than the estimated age of the BRCA1 185delAG mutation (46 generations), derived from our analogous study of BRCA1 mutations. In general, there was no evidence of multiple origins of identical BRCA2 mutations. Our study data were consistent with the previous report of a higher incidence of ovarian cancer in families with mutations in a 3.3-kb region of exon 11 (the ovarian cancer cluster region [OCCR]) (P=.10); but that higher incidence was not statistically significant. There was significant evidence that age at diagnosis of breast cancer varied by mutation (P

KW - Adult

KW - BRCA2 Protein

KW - Breast Neoplasms

KW - Breast Neoplasms, Male

KW - Evolution, Molecular

KW - Female

KW - Genetic Markers

KW - Genotype

KW - Haplotypes

KW - Humans

KW - Male

KW - Mutation

KW - Neoplasm Proteins

KW - Ovarian Neoplasms

KW - Phenotype

KW - Polymorphism, Genetic

KW - Repetitive Sequences, Nucleic Acid

KW - Transcription Factors

KW - BRCA2

KW - Breast cancer

KW - Ovarian cancer

KW - Mutation origin

KW - Cancer, breast

KW - Cancer, Ovarian

U2 - 10.1086/301885

DO - 10.1086/301885

M3 - Article

C2 - 9585613

SN - 0002-9297

VL - 62

SP - 1381

EP - 1388

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

IS - 6

ER -

Haplotype and phenotype analysis of nine recurrent BRCA2 mutations in 111 families: results of an international study

Abstract

Keywords

UN SDGs

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