Case 2:13-cv-00640-RJS Document 103-11 Filed 08/31/13 Page 3 of 6
`!CANCER RESEARCH ~4. 254R- 2S51. May 15, 1'194]
`
`Advances in Brief
`
`Evidence for Involvement of BRCAl in Sporadic Breast Carcinomas
`
`Craig S. Cropp, Heli A. Nevanlinna, Seppo Pyrhonen, Ulf-HAkan Stenman, Paul Salmikangas, Hans Albertsen,
`Ray White, and Robert Callahan
`Laboratory of Tumor l111munology and Biology, National Canur Institute, NIH. Bethesda, MD 20892 [C. C .. R. C.j; Departmeflls I and If of Obstetrics and Gynecology
`[H. A. N .. U·H. S .. P. S.j and Radiotherapy and Oncology {5. P.j, Helsinl<i University Central Hospital, HuartmaninJt.atu 2, 00290 Helsinlti, Finland; and Eccles lnstituJe of
`Human Genetic.< and lloward llughes Medica/Institute, University of Utah, Salt Lou City, Utah 84112/H. A .. R. W.f
`
`describe a high density deletion map using 17 PCR-based polymor(cid:173)
`phic STS markers located between the Dl7S250 and Dl7S579 loci in
`130 primary human breast tumors.
`
`Materials and Metbods
`
`Primary breast carcinomas and matc.bing peripheral lymphocytes were
`collected at the Helsinki University Central Hospital in Helsinki, Finland, from
`130 patients who had received no prior therapy.
`Genomic DNA was extracted and diluted to 100- 200 ng/1Jol. PCR was
`performed with 100- 200 ng template DNA, 10 mM Tris-HCl, 1.5 mM MgCI2>
`50 mM KCI, gelatin 0.1 mglml, 250 IJoM concentration of each nucleoside
`triphosphate, 0.4 unit Taq polymerase (Boehringer Mannheim), and 30 pmol of
`each primer in a total volume of 25 IJo). The PCR product was identified by end
`labeling primers with ['y-32P]ATP. All PCR reactions were performed on a
`GeneAmp PCR System 9600 starting with denaturation for 6 min at 94°C
`followed by 25 cycles of denaturation at 94•c for 10 s, annealing temperature
`for 10 s, and extension at 72"C for 20 s. The primers used, their annealing
`temperatures, and references are shown in Table I.
`The PCR products were diluted with loading buffer (95% formamide, 20
`mM EDTA, 0.05% bromophenol blue, and 0.05% xylene cyanol), beat dena(cid:173)
`tured and rapidly cooled. Samples were run in pairs (tumor and lymphocyte
`PCR product from the same patient) on a denaturing gel (7% acrylamide-32%
`fonnamide-6 M urea-1 X Tris-buffered EDTA) at a constant65-70 W. After
`electrophoresis the gel was transferred to Whatman No. 3MM paper and
`autoradiography was performed with Kodak X-Omat AR film at - 70"C.
`
`Results and Discussion
`
`Abstract
`
`The hereditary brust cancer gene BRCAJ previously has been localized
`to chromosome 17q2l. We looked for evidence of involvement of tbis
`region of chromosome 17 in 130 sporadic breast cancers. Seventeen poly(cid:173)
`morphic sequence tagged site markers were examined in these tumors
`between the Dl7S250 and Dl7S579 loci to screen for deletions as mea(cid:173)
`sured by loss or heterozygosity. The smallest common region that was
`deleted occurred in the approximately 120-ldlobase interval between the
`D17S846 and Dl7S746 loci within the BRCAJ region. Ddineatioo or this
`commonly deleted area should accelerate attempts to identify the involved
`gene(s) and its relationship to BRCA/.
`
`Introduction
`
`It is widely believed that there are one or more tumor suppressor
`genes on chromosome 17q for breast carcinoma (1-3). One candidate
`gene, BRCAJ, is genetically linked to the development of some
`familial breast cancers and is located at 17q21 (4). Ovarian cancer is
`also known to have a hereditary component (5-7). Furthermore, a
`woman with ovarian cancer is at increased risk for developing breast
`cancer as a second primary tumor, and vice versa (8- 10}. Recently,
`the syndrome for familial breast/ovarian cancer has also been linked
`to the same region as BRCAJ (11). The observed LOH 1 affecting the
`wild type chromosome in tumors from affected breast/ovarian cancer
`patients (12, 13) is consistent with the hypothesis that BRCAJ is a
`tumor suppressor gene. However, whether the target genes for familial
`breast and breast/ovarian cancers are the same or are different closely
`linked genes is not known. In a variety of hereditary neoplasias the
`affected gene (e.g., RB, TP53, APC, etc.) has also been found to be
`frequently mutated in sporadic forms of the disease (14, 15). Previ(cid:173)
`ously, we (1} and others {2, 3, 16) have shown that sporadic breast
`carcinomas are frequently affected by LOH in the general region of
`BRCAJ. The availability of additional polymorphic STS which have
`been genetically mapped to the region of chromosome 17q21 con(cid:173)
`taining BRCA 1 (17} has provided us the opportunity to further define
`the region of this portion of the genome which is affected by LOH in
`sporadic primary human breast tumors. When this study was begun
`the consensus among published reports on the genetic and physical
`boundaries of BRCAJ suggested that the centromeric boundary was
`D17S250 (18-20). The telomeric boundary was less clear. In some
`reports it was Dl7S588 while in others it was the more centromeric
`locus, Dl7S579 (19, 21, 22). In our study we chose Dl7S579 as our
`telomeric border. The interval between DJ7S250 and Dl7S579 is
`estimated to be roughly 3500 kilobases (23). In the present study we
`
`We have previously defined three regions of chromosome 17q that
`are frequently affected by LOH in primary human breast tumors (1).
`In that study a putative target gene(s) was suggested in the interval
`between Dl7S73 and NMEJ on chromosome 17q12-q21. In the
`present study we have examined an additional 17 polymorphic STS
`markers between D17S250 and Dl7S579 which is a subregion within
`the D17S73 and NMEI interval. This represents an average of one
`polymorphism every 210 kilobases since the distance between
`D17S250 and Dl7S579 is estimated to be 3500 kilobases. The total
`number of tumors examined, the percentage of the total number of
`tumors that were informative, and the percentage of the informative
`tumors which were deleted (i.e., LOH) is shown in Table 1. The
`overall frequency of LOH varies from 12 to 32% and is the highest
`between Dl7S846 and DJ7S776.
`To further define the region containing the putative target gene we
`have analyzed the genotypes of individual primary breast tumor
`DNAs for evidence of LOH. Shown in Fig. 1 are autoradiographs of
`the STS markers of four breast tumors between D 17S702 and
`D17S856. Tumor 20 showed no LOH at D17S702 and Dl7S746 but
`was deleted for the upper allele of GAS and the lower allele of
`D17S846. Markers Dl7S776 and D17S856 were not informative in
`this tumor. In tumor 26 no LOH was detected at DJ7S702, D17S846,
`and Dl7S856, but the tumor DNA was deleted for the lower allele of
`2548
`
`Received 2/24/94; accepted 4/5/94.
`The costs of publication of this article were defrayed in part by lhe paymenl of page
`charges. This article musl therefore be hereby marked advcrtisrmenr in accordance wilh
`18 U.S.C. Section 1734 solely 10 indicate this fact.
`' The abbreviations used are: LOH. loss of heterozygosity; STS, sequence tag siles;
`PCR, polymerase chain reaction
`
`Downloaded from
`
`cancerres.aacrjournals.org
`
`on August 27, 2013. © 1994 American Association for Cancer
`Research.
`
`GeneDX 1032, pg. 1
`
`

`

`Case 2:13-cv-00640-RJS Document 103-11 Filed 08/31/13 Page 4 of 6
`
`BRCAJ LN SPORADIC BREAST CARCINOMAS
`
`Table I Frequency of LOH at chro1110$ome 17q21 loci
`The locus number of tbe STS marker, the PCR annealing temperature, and a reference
`is listed for each marker used. The total number of tumors e~amined for each marker is
`indicated by N. The percentage of the total number of tumors (N) that were informative
`is shown as %1, and the numbers in parentheses are the expected heterozygosity for that
`STS marker. The percentage of tbe informative tumors (I) that were deleted is indicated
`by %LOH.
`
`LocusiSTS
`
`D/75250
`THRAJ
`Dl7S700
`Dl7S857
`Dl7S702
`GAS
`D/75846
`Dl7S746
`DJ7S776
`Dl7S856
`Dl7S648
`Dl7S855
`Dl7S902
`DI7S859
`D17S750
`Dl7SI83
`Dl7S579
`
`Annealing
`temperature
`(.C)
`
`55
`55
`60
`55
`52
`60
`55
`58
`58
`55
`60
`55
`60
`55
`65
`55
`55
`
`Ref.
`24
`25
`17
`26
`17
`27
`28
`17
`29
`26
`17
`26
`17
`26
`17
`30,31
`32
`
`N
`
`101
`95
`100
`102
`102
`97
`95
`108
`105
`103
`107
`60
`50
`49
`103
`103
`109
`
`%1
`
`80(81)
`39(81)
`54 (44)
`67 (NP)
`90(88)
`52(NP)
`78 (84)
`33 (44)
`60(55)
`51 (NP)
`36(29)
`50(NP)
`74 (78)
`35 (NP)
`57 (66)
`35 (40)
`86(87)
`
`%of
`LOH
`
`21
`27
`19
`25
`23
`26
`32
`28
`30
`19
`18
`27
`27
`12
`24
`22
`13
`
`DJ7S746. Tumor 63 was informative and unaltered at the Dl7S702,
`GAS, Dl7S846, and Dl7S856loci but was deleted for the upper allele
`of D17S776. In this patient the STS marker Dl7S746 was not infor(cid:173)
`mative. Tumor 117 was informative and unaltered at the Dl7S702,
`D17S776, and Dl7S856 loci but was deleted for the upper allele of
`Dl7S846. In this patient DJ7S746 was not informative.
`The genotypes of these four tumors and seven additional tumors for
`loci lying between Dl7S250 and D17S579 is shown in Fig. 2. Ten of
`the tumors examined in this study have clearly defined interstitial
`deletions within the BRCAJ interval, while tumor 127 appears to have
`lost a large portion of the long arm of chromosome 17. In this study
`a total of nine tumors appeared to have lost an entire chromosome 17q
`arm, since all markers in the BRCAJ region as well as telomeric
`m~~ers, such 1!5 D17S4, were ~eh:te~· ~~ ot!ter t4mors had ~OH ;lt
`all the markers in the BRCAI region but were informative and retained
`heterozygosity at D17S4. These data taken together indicate that the
`smallest commonly deleted region is located between D17S846 and
`DJ7S746. This conclusion is both consistent with and extends previ(cid:173)
`ous studies in which fewer loci were examined within the BRCA I
`region (2, 3, 16). Dl7S846 and DI7S746 are located on two overlap(cid:173)
`ping recombinant Pl bacteriophage clones. The distance between
`them is estimated to be 120-150 kilobases based on physical mapping
`data2 and could possibly contain several undiscovered genes.
`The increased availability of polymorphic STS markers in the
`region of BRCAI has also led to a continued shrinkage of the size of
`this region through genetic linkage studies in breast and breast/ovarian
`cancer families. Thus, in successive studies the telomeric border has
`moved centromerically from Dl7S579 (18, 20, 21) to DJ7S183
`(located between Dl7S750 and Dl7S579; Fig. 2) (26) to Dl7S78
`(located between Dl7S750 and DI7Sl83; Fig. 2) (33). Similarly the
`centromeric border has moved in the telomeric direction from
`Dl7S250 (19, 20, 31) to THRAJ (21, 30) to DJ7S857 (13) to DI7S702
`(34). The region we have defined as containing the target gene for
`LOH on chromosome 17q21 in sporadic breast tumors is compatible
`with these linkage studies defining BRCAI in familial breast and
`breast/ovarian cancer families. However, there is one report (29)
`which is potentially inconsistent with this conclusion. They show that
`in one family having the familial breast/ovarian cancer syndrome, one
`
`2 H. Albertsen et a/., manuscript in preparation.
`
`affected member had a recombinational event telomeric of the locu.~
`DI7S776. This locus is more telomeric than D/7S746 which is the
`telomeric boundary of the affected region defined in our study (Fig.
`2). There are at least three explanations for this apparent paradox: (a)
`the locus we have defined may be relevant only in sporadic breast
`cancer and not in hereditary breast cancer; (b) possibly there are two
`closely linked genes which are independently altered in breast-only
`versus breast/ovarian families. A comparison of the linkage studies
`done in breast-only families versus those done in breast/ovarian
`families show that in the former group the altered gene lies between
`THRAI and Dl7S579 (35), whereas in the latter group the location of
`the altered gene lies distal to Dl7S776 and proximal to Dl7S78
`(29, 32). The region we have defined is consistent with the current
`linkage analysis of the location of the altered gene in the breast-only
`families; (c) our results are not incompatible with the linkage data of
`Goldgar et al. (29). However, this would require that the BRCAJ gene
`is large (1-2 megabases) and that the recombinational event described
`by Goldgar et al. occurred within the gene. There are precedents for
`each of these requirements. For instance, the DCC gene on chromo-
`
`20
`117
`63
`26
`TL TL TL TL
`
`0175702
`
`0175746
`
`... ... ..........
`• ..- -
`-
`GAS -I
`0175846 ... -.. ... ... -...
`--
`-
`.....
`...
`... .......
`
`0175776
`
`I
`.
`""(: ~
`. ,,, .
`.... .
`0175856 -
`...
`
`"
`
`~
`
`6- ~
`
`Fig. I. Autoradiographs of four tumors for the six STS polymorphic markers between
`D/7S702 and D/75856. Arrows, deleted allele indicating LOH. Tumor 20 is deleted for
`GAS and DI7S846; tumor 26 is deleted for DI7S746, tumor 63 is deleted for Dl7Sn6;
`and tumor 117 is deleted for 0175846. T, tumor; L, lymphocyte.
`2549
`
`Downloaded from
`
`cancerres.aacrjournals.org
`
`on August 27, 2013. © 1994 American Association for Cancer
`Research.
`
`GeneDX 1032, pg. 2
`
`

`

`Case 2:13-cv-00640-RJS Document 103-11 Filed 08/31/13 Page 5 of 6
`
`BRCAI IN SPORADIC BREAST CARCINOMAS
`
`PRa!E
`
`TI.M:R
`
`Fig. 2. Genoty~ of lltumors between STS
`markers D17S250 and DJ7S579. e. markers
`with LOH {i.e., deleted); 0, STS markers whicb
`are informative and normal; e. either the tumor
`was not examined for that marker, or the marker
`was not informative. The commonly deleted
`region is indicated at the right side of the figute.
`The genetic order of the STS marker probes is
`according to published linkage studies (17, 26).
`
`11.2
`
`12
`
`21.1
`21.2
`
`21.3
`
`22
`
`23
`
`24
`
`25
`
`17Q
`
`0175250
`n ttA1
`
`0175857
`
`0175702
`GAS
`
`0175746
`
`0175776
`
`0175856
`
`0175855
`
`017S902
`
`0175579
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0 Informative and retention of heterzygosity
`
`44
`
`62
`
`89
`
`130
`
`20
`
`26
`
`63
`
`16
`0
`
`117 30
`0
`
`127
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0
`
`0 0
`
`0
`
`0
`
`0
`
`0 • • 0
`0 • • 0
`0 • • • • • • • • • 0
`0175700 • • 0 • 0
`0 • 0 • 0
`0 • 0
`0 • 0
`0 •
`0 • 0
`0 0 •
`0 0 • • • • • 0 • • •
`0175846 • • • • • • 0
`0 • • • I~
`0 • • 0 • 0 • • • • •
`0 • 0
`0 • • • 0 • •
`0 • 0 • 0
`0 •
`0 • • • • • 0 • •
`0175648 • 0
`0 • 0 • • 0 • • • • •
`0 • • 0
`0 • 0 •
`017S859 • • 0 • • • • • • • •
`0175750 • 0
`0 • 0 • • •
`0175183 • • • • • 0
`0 • 0 • •
`0 •
`0 • 0
`• Deleted
`• Not informative or not done
`
`some 18q is approximately 1.4 megabase5 (36), and the Duchenne
`muscular dystrophy (DMD) gene on Xp21 is approximately 2.3
`megabases (37). In the search for the DMD gene, linkage analysis was
`somewhat confusing because of the frequency of recombination
`events within such a large gene (38-40). aearly, identification of the
`target gene(s) in sporadic breast carcinomas as well as the familial
`breast and breast/ovarian carcinoma loci will be required to distin(cid:173)
`guish between these possibilities.
`
`References
`
`1. Cropp, C. S., Ol.ampeme, M-H., Lidereau, R., and Callahan, R. Identification of three
`regioos on chromosome 17q in primary human breast carcinomas wbicb are fre(cid:173)
`quently deleted. Cancer Res., 53: 5617-5619, 1993.
`2. Camelis. R. S., Devilee, P .• van Vliet. M., Kuipers-Dijkshoom, N., Kersenmaeker, A.,
`Bardoel, A., Meera Khan, P., and Comelisse, C. J. Allele loss patterns on chrom()(cid:173)
`some 17q in 109 breast carcinomas indicate at least two distinct target regions.
`Onoogene, 8: 781-785, 1993.
`3. Saito, H., lnazawa. J., Saito, S., Kaswni, F., Koi, S., Sagae, S., Kudo, R., Saito, J.,
`Noda, K., and Nakamura, Y. Detailed deletion mapping of chromosome 17q in
`ovarian and breast cancers: 2-cM region on 17q21.3 often and commonly deleted in
`tumors. cancer Res., 53: 3382-3385, 1993.
`4. Hall, J. M., Lee, M. K., Newman, B., Horrow, J. E., Anderson, L.A., Huey, B., and
`King, M. C. Linkage of early-onset familial breast cancer to chromosome 17q21.
`Science (Washington DC), 250: 1684-1689, !990.
`5. DiCioccio, R. A., and Piver, M.S. The genetics of ovarian cancer. Cancer Invest.. 10:
`135-141, 1992.
`6. Matheson, J. A. B., Matheson, H., and Anderson, S. A. Familial ovarian cancer. How
`rare is it? J. R. CoU. Gen. Pract., 31: 743-745, 1981.
`7. Perez. R. P., Godwin, A. K., HAmilton, T. C., and Ozols, R. F. Ovarian cancer
`biology. Semin. Oncol., 18: 186- 204, 1991.
`8. Curtis, R. E., Hoover, R. N., Kleinerman, R. A., and Harvey, E. B. Second cancer
`following cancer of the fe.rnale genital system in Connecticut, 1935-82. Nat!. cancer
`lnst. Mooogr., 68: 113-137, 1985.
`9. Harvey, E. B .• and Brinton. L A. Second cancer foUowing cancer of the breast in
`Connecticut, 1935-1982. Nat!. Cancer lost. Monogr., 68: 99-112, 1985.
`10. Curtis, R. E., Boice, J.D., Jr., Kleinerman, R. A., Flannery, J. T., and Fraumeni, J. F.,
`Jr. Summary: multiple primary cancers in Connecticut, 1935-82. Nat!. Cancer inst.
`Monogr., 68: 219- 242, 1985.
`II. Narod, S. A., Feunteun, J., lynch, H . T., Watson, P., Conway, T., l ynch, J., and
`Lenoir, G. M. Familial breast-ovarian cancer locus on chromosome 17q12-q23.
`Lancet, 338: 82-83, 1991.
`12. Smith, A. A., Easton. D. F., Evans, D. G. R., and Ponder, B. A. J. Allele losses in the
`region 17q12-21 in familial breast and ovarian cancer involve the wild-type chro(cid:173)
`mosome. Nat. Genet., 2: 128- 131, 1992.
`13. Kelsell, D. P., Black. D. M., Bishop, P. T., and Spurr, N. K. Genetic analysis of the
`BRCA1 region in a large breast/ovarian family: refinement of tbe minimal region
`2550
`
`containing BRCAl. Hum. Mol. Genet., 2: 1823-1828, 1993.
`14. Ponder, B. A. J. Molecular genetics of cancer. Br. Med. J., 304: 1234-1236, 1992.
`15. Finlay, G. J. Genetics, molecular biology and colorectal cancer. Mutat. Res., 290:
`3-12, 1993.
`16. Futreal, P. A., Soderkvist. P., Marks, J. R., Iglehart, J. D., Cochran, C., Barrett, J. C.,
`and Wiseman, R. W. Detection of frequent allelic loss on proximal cbromosme 17q
`in sporadic breast carcinoma using microsatellite length polymorpbisms. cancer Res.,
`52: 2624-2627, 1992.
`17. Albertsen, H., Plaetke, R., Ballard, L, Fujimoto, E., Connolly, J., Lawrence, E.,
`Rodriguez, P., Robertson, M., Bradley, P., Milner, B., Fuhrman, D., Marks, A,
`Sargent. R., Cartwright. P., Matsunami, N., and White, R. Genetic mapping of the
`BRCAI region on chromosome 17q21. Am. 1. Hum. Genet., in press. 1994.
`18. Devilee, P., Camelis, R. S., Bootsma, A., Bardoel, A., van Vliet. M., van Leeuwen,
`I., Oeton, F. J., de Klein, A., Lindbout. D., Vasco, H. F. A., Cornel.i.sse, C. J., and
`Khan, P.M. Linkage to markers for the chromosome region 17ql2-21 in 13 Dutch
`breast cancer kindreds. Am. J. Hum. Genet., 52: 730-735, 1993.
`19. Smith, S. A., Easton, D. F., Ford, D. Peto, J., Anderson, K., Averill, D., Stranon, M.,
`Ponder, M., Pye, C., and Ponder, B. A. J. Genetic heterogeneity and localization of
`a familial breast-ovarian cancer gene on chromosome 17ql2-21. Am. J. Hwn. Genet.,
`52: 767- n6, 1993.
`20. Spurr, N. K., Kelsell, D. P., Black, D. M., Murday, V. A., Turner, G., Crockford,
`G. P., Solomon, E., Cartwright. R. A., and Bishop, D. T. Linkage analysis of
`early-onset breast and ovarian cancer families, with markers on tbe long arm of
`chromosome 17. Am. J. Hum. Genet., 52: 777- 785, 1993.
`21. Goldgar, D. E., Cannon·Albrigbt, L. A., Oliphant. A, Ward, J. H., Linker, G.,
`Sweosen. J. H., Tran, T. D., Fields, P., Ubaniet. P., and Skolnick, M. H. Olrolll0$0me
`17q linkage studies of 18 Utah breast cancer kindreds. Am. J. Hum. Genet, 52:
`743-748, 1993.
`22. Chamberlain, J. S., Boehnke, M., Frank, T. S., Kiousis, S., Xu, J., Guo, S-W., Hauser,
`E. R., Narum, R. A., Helmbold, E. A., Markel, D. S., Kesbavarzi, S. M., Jackson,
`C. E., Ca!zone, K., Garber, J., Collins, F. S., and Weber, B. L. BRCAI maps proxllllal
`to D17SS79 on chromosome 17q21 by genetic analysis. Am. J. Hum. Genet., 52:
`792-798, 1993.
`23. Abel, K. J., Boehnke, M., Prabalad, M., Ho, P., Flejter, W . L., Watkins, M .,
`VanderStoep, J., Cbandrasekharappa, S.C., Collins, F. S., Glover, T. W., and Weber,
`B. L A radiation hybrid map of tbe BRCA1 region of chromosome 17q12-21.
`Geoomics, 17: 632-641, 1993.
`24. Weber, J. l., Kwitek, A. E., May, P. E., Wallace, M. R., Collins, F. S., and Ledbetler,
`D. H. Dinucleotide repeat polymorpbisms at the D17S2SO and D17S261loci. Nucleic
`Acids Res., 18: 4640, 1990.
`25. Futreal, P. A., Barrett, J. C., and Wiseman, R. W . Dinucleotide repeat polymorphism
`in the THRA.l gene. Hum. Mol. Genet., 1: 66, 1992.
`26. Anderson, L A., Friedman, L., Osborne-Lawrence, S., Lyncb, E., Weissenba.ch, J.,
`Bowooc:k, A., and King, M-C. High-density genetic map of tbe BRCAI region of
`chromosome 17q12-q21. GellOIIlics, 17: 6 18-623, 1993.
`27. Epstein, N., Nahor, 0., and Silver, J. The 3' ends of alu repeats are highly polymor(cid:173)
`phic. Nucleic Acids Res., 18: 4634, 1990.
`28. Flejter, W. L, Kukowska-latallo, J. F., Klousis, S., Cbandrasekharappa, S.C., King,
`S. E., and Chamberlain, J. S. Tetranucleotide repeat polymorphism at D17S846 maps
`
`Downloaded from
`
`cancerres.aacrjournals.org
`
`on August 27, 2013. © 1994 American Association for Cancer
`Research.
`
`GeneDX 1032, pg. 3
`
`

`

`Case 2:13-cv-00640-RJS Document 103-11 Filed 08/31/13 Page 6 of 6
`BRCAI IN SPORAOIC BREAST CARCINOMAS
`
`within 40 kb of GAS at 17q12--22. Hum. Mol. Genet., 2: 1080, 1993.
`29. Goldgar, D. E., Fields, P., Lewis, C. M., Trao, T. D., Cannon-Albright, 1.. A., Ward,
`J. H., Swensen, J., and Skolnick, M. H. A large kiDdred wit.b 17q-linked breut and
`ovarian c:aocer: genetic pbeootypic, and genealogical analysis. J. Nail. Cancer lnst.,
`86: 200-209, 1994.
`30. Black, D. M., Nicolai, H., Borrow, J., and Solomon, E. A somatic cell hybrid map of
`tbe long arm of human chromosome 17, containing lhe familial breut cancer locus
`(BRCAI). Am. J. Hum. Genet., 52: 702-710, 1993.
`31. Easton, D. F., Bishop, D. T., Ford, D., Crockford, G. P., and Consortium, B. C. L.
`Genetic linka&e analysis in familial breut and ovuy c:aocer--f'eSults from 214
`families. Am. J. Hum. Genc:L, 52: 678-701, 1993.
`32. IWI, J. M., Friedman, L., Gueot.ber, C., Lee, M. K., Weber, J. L., Black, D. M., and
`King. M-C. Oosi.og in on a breast C&D<:Cr gene: on chromosome 17q. Am. J. Genet ..
`50: 1235-1242, 1992.
`33. Simllld J., F., J., Linoir, 0., Tonin, P., Normand, T., The, V. L., Vivier, A., Lasko, D.,
`Morgan. K., Rouleau, 0. A., Lyoch, H., Labrie, F., llld Narod, S. A. Genetic mapping
`of t.be breut-<>variao cancer syndrome to a small interval on chromosome 17q12-21:
`exclusionofCIJididategenesEDHI7B2andRARA. Hum. Mol. Genet.,2: 1193-1199,
`1993.
`34. Smith, S. A., DiCioccio, R. A., Struewiug. J. P., Easton, D. F., Gallion, H. H.,
`Albertsen, H., Mawyer, S., Johansson, B., Steic:hen-Gersdorf, E., Stranon, M., Ford,
`D., Marshall, G., White, R. I.., Piver, M. S., and Ponder, B. A. J. Localization of
`
`the breast-<>varian cancer susceptibility gene (BRCAI) on 17q 12-21 to and interval of
`:SI eM. Genes Chromosomes Cancer, 10: in press, 1994.
`35. Bowcock, A. M., Andenon, L.A., Friedmlll, L. S., Black, D. M., Osborne-Lawrence,
`S .. Rowell, S. E., Hall, J. M., Solomon, E., and King. M-C. THRAl and D17Sl83
`flank an interval of <4 eM for the breast-<>varian cancer gene (BRCA I) on chroiJIO-.
`some 17q2l. Am. J. Hum. Genet., 52: 718-722, 1993.
`36. Cho, K. R., Oliner, J.D., Simons, J. W., Hedrick, L., Fearon, E. R., Preisioger, A. C ..
`Hedge, P., Silverman. G. A., and Vogclstein, B. The DCC gene: struc!ural analysis
`and mutations in coloredal c:arcinomas. Geoomics, /9: 525-531, 1994.
`37. Worton. R. G. Duchenne muscular dystrophy: gene and gene product; mechanism of
`mutation in t.be gene. J. Iober. Metab. Dis. 15: 539-550, 1992.
`38. Koenig, M., Hoffman, E. P., Bertelson. C. J., Monaco, A. P., Feener, C., and Kunkel,
`L. M. Complete cloning of Ouchenne muscular dystrophy (DMD) eDNA and pre(cid:173)
`liminary genomic organization of t.be DMD gene in normal and affeCted individuals.
`Cell, 50: 509-517, 1987.
`39. Fischbeck, K. H •• Riner, A. W .• Tirsc:hwell, D. I.., Kunkel, I.. M .. Bertelson.
`C. J., Monaco, A. P., Hejtmancik, J. F .• Boehm, C., lonasescu, V., lonasescu, R.,
`Pericak-Vancc:, M., Kandt. R., and Roses, A. D. Reoombination with PERT87
`(DXSJ64) in families with X-linked muscular dystrophy. Lancet, 2: 104, 1986.
`40. Kunkel, L. M., et aL Analysis of deletions in DNA from patients with Becker and
`Ducbenne muscular dystrophy. Nature (Lond.), 322: 73-n, 1986.
`
`Downloaded from
`
`cancerres.aacrjournals.org
`
`on August 27, 2013. © 1994 American Association for Cancer
`Research.
`
`2551
`
`GeneDX 1032, pg. 4
`
`