ライフサイエンスコーパス: germline mutation

1 s identified in 1 patient in addition to the germline mutation.

2 ly, which also carried a segregating SMARCA4 germline mutation.

3 t 'signature' mutations, never seen as a TSC germline mutation.

4 lead to the suspicion and confirmation of a germline mutation.

5 sional and nonlesional skin confirmed a BAP1 germline mutation.

6 tic lesions raised concerns about a possible germline mutation.

7 occurred in two patients with identified RB1 germline mutation.

8 ning patients with a history suggestive of a germline mutation.

9 riampullary neoplasms also had a deleterious germline mutation.

10 atients with HGSC with either BRCA1 or BRCA2 germline mutation.

11 Two patients exhibited LZTR1 germline mutations.

12 has potential for the targeted correction of germline mutations.

13 rther increased by already present oncogenic germline mutations.

14 redisposition syndromes, for the presence of germline mutations.

15 molecular signature identified 9 additional germline mutations.

16 rome when they were found to have pathogenic germline mutations.

17 ases, especially those caused by deleterious germline mutations.

18 nts with pancreatic cancer had a deleterious germline mutation, 31 (3.5%) of which affected known fam

19 did not consent, an estimated 5.3 of 102 had germline mutations (5.2%; 95% CI, 2.0% to 17.5%).

20 Observations: BRCA1 and BRCA2 germline mutations account for up to 30% of inheritable

21 Germline mutations affecting the CBM complex are now rec

22 g the 4 patients with pineoblastoma, all had germline mutation and 2 had family history of retinoblas

23 ases did not show a known correlation of the germline mutation and a known syndrome.

24 DNA lesions that evade repair and result in germline mutation and paves the way for similarly compre

25 ncers have not been found to have pathogenic germline mutations and are considered to have Lynch-like

26 s been implied in studies describing de novo germline mutations and copy number variants.

27 of being transmitted to offspring as de novo germline mutations and, in principle, can provide insigh

28 s (4 with biallelic somatic loss, and 3 with germline mutations) and 4 of 5 with ATM aberrations.

29 Germline mutations are a driving force behind genome evo

30 The clinical consequences of PMS2 germline mutations are poorly understood compared with o

31 Carriers of BRCA1 germline mutations are predisposed to breast and ovarian

32 Germline mutations are the principal cause of heritable

33 Germline mutations are the source of evolution and contr

34 These data implicate this PARK2 germline mutation as a genetic susceptibility factor for

35 Meiosis is a potentially important source of germline mutations, as sites of meiotic recombination ex

36 y outcome was identification of a pathogenic germline mutation associated with cancer predisposition.

37 h CRC at age younger than 50 years carries a germline mutation associated with cancer; nearly half of

38 Only 43 of the 85 subjects with germline mutations associated with a hereditary cancer s

39 in we report analyses of 160 BRCA1 and BRCA2 germline mutation-associated breast and ovarian tumors.

40 However, not all BRCA1 and BRCA2 germline mutation-associated tumors respond.

41 Genetic screening for a germline mutation at the RET gene was performed in 11 fa

42 We also identified de novo germline mutations at identical positions in two childre

43 py regimen, patients without BRCA1 and BRCA2 germline mutations benefited from the addition of carbop

44 travenous chemotherapy is generally used for germline mutation (bilateral, familial) retinoblastoma w

45 We identified a germline mutation c.1681C>T (p.Arg561Cys) in platelet-de

46 led heterozygosity for the recurrent de novo germline mutation, c.148G > A, p.Asp50Asn.

47 arly identification of individuals who carry germline mutations can affect clinical care not only for

48 t clinical utility of baseline WBMRI in TP53 germline mutation carriers and may form an integral part

49 ble estimates of cancer risk and spectrum in germline mutation carriers are essential for management.

50 prevalence of SDHA, TMEM127, MAX, and SDHAF2 germline mutation carriers from 1993 to 2016.

51 = .02) and remained significant when BRCA1/2 germline mutations carriers were excluded (P = .021).

52 tations have been described in many cancers, germline mutations cause Costello syndrome (CS), a conge

53 d individual-derived iPSCs showed that these germline mutations caused aberrant splicing of the endog

54 from work identifying rare, highly penetrant germline mutations causing 'hereditary' cancer.

55 d expansion in primates-can introduce unique germline mutation clusters that can play a role in prima

56 e of thyroid cancer in CS patients with SDHx germline mutations compared to those with PTEN mutations

57 rogenase genes (SDHx) co-occurring with PTEN germline mutations confer a 2-fold increased prevalence

58 Genes in which germline mutations confer highly or moderately increased

59 not attributable to MLH1 hypermethylation or germline mutations contain 2 or more somatic mutations i

60 Purpose Deleterious germline mutations contribute to pancreatic cancer susce

61 Proportion of clinically actionable germline mutations detected by universal tumor-normal se

62 The frequency of germline mutations detected by using NGS has been report

63 Germline mutation determines rates of molecular evolutio

64 families where probands lacked nonsynonymous germline mutations, especially in genes intolerant to mu

65 ence of dysplastic nevus syndrome and a BAP1 germline mutation extends the spectrum of the BAP1 tumor

66 similar to nonsense (NS) and frameshift (FS) germline mutations found in warts, hypogammaglobulinemia

67 The biology of neoplasia caused by germline mutations has led to paradigm-changing precisio

68 Study of the biology of tumors caused by germline mutations has led to recent paradigm-changing t

69 Germline mutations have been identified in at least 20 g

70 cted by colorectal adenomatous polyposis, no germline mutations have been identified in the previousl

71 nd ovarian cancer patients harboring BRCA1/2 germline mutations have clinically benefitted from thera

72 genitor cells (NPCs) to demonstrate that NF1 germline mutations have dramatic effects on neurofibromi

73 he p.Thr354Met, p.Thr355del, and p.Arg396Gln germline mutations impair GATA2 promoter activation.

74 Most patients carry a germline mutation in 1 allele of the MMR genes MSH2 or M

75 th breast cancer, 10.7% were found to have a germline mutation in a gene that predisposes women to br

76 oma viral oncogene homolog (KRAS)-variant, a germline mutation in a microRNA-binding site in KRAS, is

77 Here we identify the SEMA4A p.Val78Met germline mutation in an Austrian kindred with FCCTX, usi

78 We describe the first kindred to date with a germline mutation in BAP1 associated with multiple cutan

79 BL syndrome caused by a heterozygous de novo germline mutation in CBL codon D390.

80 Women who carry a germline mutation in either the BRCA1 or BRCA2 gene face

81 mately 70% of DC cases are associated with a germline mutation in one of nine genes, the products of

82 loping colorectal tumors (CRTs) because of a germline mutation in one of their mismatch repair (MMR)

83 f tumors in multiple organs and is caused by germline mutation in one of two tumor suppressor genes,

84 Here, we show that c.823C>T (p.Arg275Trp), a germline mutation in PARK2, is present in a family with

85 rtance of the recently discovered E318K MITF germline mutation in patients with multiple primary mela

86 ly led to the identification of a truncating germline mutation in RPS20, which encodes a component (S

87 n, and his 13-year-old daughter, revealing a germline mutation in the BAP1 gene (c.592G>T, p.Glu198X)

88 ritable pulmonary arterial hypertension with germline mutation in the bone morphogenetic protein rece

89 The efficiency of site-specific germline mutation in the mouse confirm TALEN mediated mu

90 Germline mutation in the NF1 tumor suppressor gene under

91 Caused by a germline mutation in the NF1 tumor suppressor gene, indi

92 conclude that a homozygous loss-of-function germline mutation in the NTHL1 gene predisposes to a new

93 Mice expressing a germline mutation in the phospholipase C-gamma1-binding

94 In total, 1 in 1000 individuals carries a germline mutation in the PKD1 or PKD2 gene, which leads

95 Mice bearing a germline mutation in the RAS binding domain of the p110a

96 ominant disorder in which patients inherit a germline mutation in the tumor-suppressor gene Patched (

97 sk to an individual of carrying a pathogenic germline mutation in three mismatch repair (MMR) genes:

98 od, and genetic testing identified a de novo germline mutation in TMEM173, confirming a diagnosis of

99 Finally, a loss-of-function germline mutation in UBE2T was detected in a high-risk b

100 otes or compound heterozygotes for the R200W germline mutation in VHL have Chuvash polycythemia, wher

101 Patients with a germline mutation in von Hippel-Lindau (VHL) develop ren

102 Germline mutations in 14 genes have been associated with

103 First, patients with germline mutations in adenomatous polyposis coli (APC) a

104 tify the complementation group and biallelic germline mutations in all 27 families: FANCA (7), FANCB

105 blood samples were genotyped for somatic and germline mutations in APC and CTNNB1.

106 We investigated the prevalence of germline mutations in APC, ATM, BRCA1, BRCA2, CDKN2A, ML

107 Germline mutations in ATM (encoding the DNA-damage signa

108 To describe 8 new families with germline mutations in BAP1 and provide a comprehensive r

109 Individuals harboring inherited heterozygous germline mutations in BAP1 are predisposed to a range of

110 Patients with germline mutations in BAP1 may develop several flesh-col

111 Our results indicate that germline mutations in both coding and noncoding regions

112 Loss-of-function germline mutations in BRCA1 (MIM #113705) confer markedl

113 Germline mutations in BRCA1 and BRCA2 are relatively com

114 Germline mutations in BRCA1 and BRCA2 predispose to comm

115 Data herein demonstrate that germline mutations in Brca1 impair luminal cell lineage

116 types occurring in patients with deleterious germline mutations in BRCA1 or BRCA2 seem to be particul

117 Germline mutations in BRCA1 predispose carriers to a hig

118 DNA samples were analyzed for germline mutations in BRCA1, BRCA2, and 16 other cancer

119 Testing for germline mutations in BRCA1/2 is standard for select pat

120 Heterozygous germline mutations in breast cancer 1 (BRCA1) strongly p

121 amilies with a history of CRC, we associated germline mutations in BRF1 with predisposition to CRC.

122 Inactivating germline mutations in BTK cause a severe B-cell defect a

123 To quantify the role of germline mutations in cancer susceptibility, we applied

124 Germline mutations in cancer-predisposing genes were ide

125 Both carried homozygous germline mutations in CARD11 (p.Cys150*), impairing NF-k

126 Germline mutations in CDKN2A are frequently identified a

127 The role of germline mutations in children and adults with hematolog

128 usceptibility locus to 2q37.1 and identified germline mutations in DIS3L2, a homolog of the Schizosac

129 cluded owing to subsequent identification of germline mutations in DNA mismatch repair genes (n = 47)

130 Although the prevalence of germline mutations in DNA-repair genes among men with lo

131 Overall, the frequency of germline mutations in DNA-repair genes among men with me

132 The frequencies of germline mutations in DNA-repair genes among men with me

133 Additional factors, such as germline mutations in drug-metabolizing enzymes and othe

134 Tumors arising in patients who carry germline mutations in either BRCA1 or BRCA2 are sensitiv

135 Germline mutations in established moderately or highly p

136 DNA from patients was analyzed for germline mutations in four telomere maintenance genes as

137 plastic syndrome (MDS) and monosomy 7 harbor germline mutations in GATA2.

138 tients with OC, 347 (18%) carried pathogenic germline mutations in genes associated with OC risk.

139 h tumors that have deficiency in MMR, but no germline mutations in genes encoding MMR proteins.

140 transcription has been linked to cancer, and germline mutations in genes encoding Pol III subunits or

141 ately 5% of all CRCs arise in the setting of germline mutations in genes involved in key cellular pro

142 In our multicenter study, the incidence of germline mutations in genes mediating DNA-repair process

143 sorders are caused by biallelic inactivating germline mutations in genes such as RAB27A (GS) and PRF1

144 es are significantly associated with risk of germline mutations in hamartomatous-polyposis associated

145 sonalize HR directed therapies in the clinic.Germline mutations in homologous recombination (HR) DNA

146 ides a centralized workflow for prioritizing germline mutations in human disease within a streamlined

147 We report germline mutations in human Piwi (Hiwi) in patients with

148 a natural background dataset for amino acid germline mutations in humans.

149 llows for the detection of BRCA and non-BRCA germline mutations in individuals with high risks of bre

150 We identified germline mutations in MET, encoding a receptor tyrosine

151 Patients with bi-allelic germline mutations in mismatch repair (MMR) genes (MLH1,

152 quired somatic mutations in patients without germline mutations in MMR genes using next-generation se

153 s, without hypermethylation of MLH1), but no germline mutations in MMR genes.

154 for Lynch syndrome, yet have no identifiable germline mutations in MMR genes.

155 These findings describe germline mutations in NFKB2 and establish the noncanonic

156 ng in the four remaining families identified germline mutations in noncoding sequences surrounding AC

157 iated with risk for colorectal cancer (CRC); germline mutations in NTHL1, RPS20, FANCM, FAN1, TP53, B

158 eature facilitated CRISPR-Cas9 generation of germline mutations in orco, the gene that encodes the ob

159 Whether germline mutations in other breast cancer susceptibility

160 Conclusion Germline mutations in pancreatic cancer susceptibility g

161 ation in individuals with MLH1 IHC loss, and germline mutations in patients exhibiting loss of MSH6,

162 Methods To define the prevalence of these germline mutations in patients with apparently sporadic

163 Patients with heterozygous germline mutations in phosphatase and tensin homolog del

164 Heterozygous germline mutations in PHOX2B, a transcriptional regulato

165 Patients harboring heterozygous germline mutations in PRKCSH are thought to develop rena

166 Germline mutations in PTEN have been described in a spec

167 Germline mutations in PTEN on 10q23 were found to cause

168 Caused by germline mutations in PTEN, PHTS also causes increased r

169 0% vs 2%; P = .003) were more likely to have germline mutations in PTEN.

170 e (CS), a disorder typically associated with germline mutations in PTEN.

171 Germline mutations in Ras pathway components are associa

172 r869, Gly870, Ile871 and Asp880, which match germline mutations in Schinzel-Giedion syndrome (SGS), w

173 ted GISTs are SDHB-deficient with underlying germline mutations in SDH subunits A-D.

174 Patients with Lynch syndrome carry germline mutations in single alleles of genes encoding t

175 After discovering segregating deleterious germline mutations in SMARCA4 in all three families, we

176 We identified biallelic germline mutations in SPRTN (also called C1orf124 or DVC

177 Germline mutations in SPRTN cause Ruijs-Aalfs syndrome (

178 and the identification of patients carrying germline mutations in STAT1, STAT3, and STAT5B have high

179 Recently, germline mutations in STAT3 have also been associated wi

180 Our findings identify germline mutations in telomerase as a Mendelian risk fac

181 Germline mutations in telomere biology genes cause dyske

182 ively referred to as TBD here) are caused by germline mutations in telomere biology genes leading to

183 ifetime cancer risks conferred by pathogenic germline mutations in that gene.

184 Germline mutations in the BRCA1 and BRCA2 breast cancer

185 Cancers due to germline mutations in the BRCA1 gene tend to lack target

186 Germline mutations in the cadherin 1, type 1, E-cadherin

187 te myeloid leukemia (AML) syndrome caused by germline mutations in the DEAD/H-box helicase gene DDX41

188 HDGC, which is mainly caused by germline mutations in the E-cadherin gene (CDH1), render

189 eutropenia is usually caused by heterozygous germline mutations in the ELANE gene encoding neutrophil

190 Germline mutations in the Folliculin (FLCN) tumour suppr

191 Germline mutations in the gene encoding the tumor suppre

192 Germline mutations in the gene encoding tumor suppressor

193 Here, we report that germline mutations in the inflammasome sensor NLRP1 caus

194 t colorectal cancer (CRC) have no detectable germline mutations in the known cancer predisposition ge

195 Lynch syndrome is caused by germline mutations in the mismatch repair (MMR) genes.

196 Lynch syndrome, caused by germline mutations in the mismatch repair genes, is asso

197 compound-heterozygous loss-of-function (LoF) germline mutations in the mismatch-repair gene MSH3.

198 mal dominant genetic disorder resulting from germline mutations in the NF2 gene.

199 ent protocol for the generation of heritable germline mutations in the parasitoid jewel wasp, Nasonia

200 ion (HO) caused by heterozygous inactivating germline mutations in the paternal allele of the GNAS ge

201 Germline mutations in the PTEN tumor-suppressor gene and

202 minant, hereditary cancer disorder caused by germline mutations in the RET (formerly MEN2A, MEN2B) pr

203 Ionizing radiation (IR) and germline mutations in the retinoblastoma tumor suppresso

204 Prevalence and spectra of germline mutations in the SDHA, TMEM127, MAX, and SDHAF2

205 umeni syndrome, which results primarily from germline mutations in the TP53 gene.

206 Somatic or germline mutations in the tuberous sclerosis complex (TS

207 common tumor-predisposition disorder due to germline mutations in the tumor suppressor gene NF1.

208 lection of genetic disorders associated with germline mutations in the tumor suppressor gene PTEN.

209 Germline mutations in the tumor suppressor Pten are a we

210 d in several skin-tumour syndromes caused by germline mutations in the tumour suppressor gene, CYLD.

211 identify the first FA patient with biallelic germline mutations in the ubiquitin E2 conjugase UBE2T.

212 adenomatous polyposis (FAP-iPSCs) harboring germline mutations in the WNT-signaling-pathway-regulato

213 Germline mutations in the X-linked gene, methyl-CpG-bind

214 Heterozygous germline mutations in the zinc finger transcription fact

215 ical management guidelines for patients with germline mutations in these 4 newly included genes are l

216 ar, generating several independent heritable germline mutations in this gene.

217 sease caused by high-penetrance heterozygous germline mutations in TNFAIP3, which encodes the NF-kapp

218 s a cancer predisposition disorder caused by germline mutations in TP53 that can lead to increased mi

219 lies with the Li-Fraumeni syndrome who carry germline mutations in TP53, the gene encoding the tumor-

220 ncer predisposition syndrome associated with germline mutations in TP53.

221 In humans, germline mutations in Trpm6 cause autosomal dominant hyp

222 osis and Noonan and Legius syndromes, harbor germline mutations in various RAS/mitogen-activated prot

223 Constitutional (germline) mutations in any of three genes, KRIT1, CCM2 a

224 al tumors who had 2 or more somatic (but not germline) mutations in genes encoding MMR proteins (doub

225 trial tumors with 2 or more somatic (but not germline) mutations in MMR proteins also have mutations

226 contain a larger-than-expected proportion of germline mutations, including previously unreported muta

227 rehensive genome-wide survey of the range of germline mutations induced in laboratory mice after pare

228 phenomenon where the pathogenic effect of a germline mutation is corrected by a second somatic event

229 checkpoint regulator, and the CHEK2*1100delC germline mutation leads to loss of function and increase

230 cancers with MMR deficiency not explained by germline mutations might undergo analysis for tumor muta

231 Pathogenic germline mutations occurred in eight PCC/PGL susceptibil

232 Germline mutation of Bmi1 significantly reduced both the

233 We report here that germline mutation of Brca1 in p18-deficient mice blocks

234 Alternately, germline mutation of Brca1 shifts the fate of luminal ce

235 Germline mutation of BRCA2 induces hereditary pancreatic

236 Germline mutation of the BRCA1 associated protein-1 (BAP

237 Although the linkage between germline mutations of BRCA1 and hereditary breast/ovaria

238 In addition, two germline mutations of BRCA1 are found to disrupt the dim

239 Individuals with germline mutations of C/EBPepsilon fail to develop norma

240 (WES) has the potential to reveal tumor and germline mutations of clinical relevance, but the diagno

241 ] age, 41.0 [13.3] years), 58 (6.0%) carried germline mutations of interest, including 29 SDHA, 20 TM

242 tely 90% of patients carry either somatic or germline mutations of PTPN-11, K-RAS, N-RAS, CBL, or NF1

243 Germline mutations of the BRCA1-associated protein-1 gen

244 ullary thyroid cancer (MTC) can be caused by germline mutations of the RET proto-oncogene or occurs a

245 Germline mutations of the retinoblastoma gene (RB1) pred

246 Germline mutations of the SMARCB1 gene predispose to two

247 In this study, we assay the impact of rare germline mutations on CRC, analysing high-coverage exome

248 e in investigating the impact of somatic and germline mutations on miRNA function in cancer.

249 % of the MMR-deficient tumors without causal germline mutations or promoter methylation.

250 We report on two germline mutations (p.Gly39dup and p.Val55Met) in RRAS,

251 equencing identified two homozygous missense germline mutations, P733L and P832S, in the JAK1 protein

252 The mechanisms by which SMARCB1 germline mutations predispose to rhabdoid tumors versus

253 most two orders of magnitude higher than the germline mutation rate and that both mutation rates are

254 first time we determined the genome-wide STR germline mutation rate from a deeply sequenced human ped

255 The germline mutation rate has been extensively studied and

256 us to make the first direct comparison with germline mutation rates in these two species.

257 into question by revealing unexpectedly low germline mutation rates, which imply that substitutions

258 omatic mutations; frequencies of deleterious germline mutations related to patient phenotype and inci

259 one unrelated individual with biallelic PMS2 germline mutations, representing constitutional mismatch

260 ts with breast cancer in the NYBCS carried a germline mutation responsible for their disease: 11.0% (

261 ied, and whole-exome sequencing identified a germline mutation (S631G) at a highly conserved serine r

262 We introduce Germline Mutation Scoring Tool fOr Next-generation sEque

263 utations, we found remarkable consistency in germline mutation spectra between the sexes and at diffe

264 To determine whether BRCA1 and BRCA2 germline mutation status affects therapy response in pat

265 Whether BRCA1 and BRCA2 germline mutation status affects treatment outcome remai

266 Prediction of germline mutation status was compared for combinations o

267 uvant treatment according to BRCA1 and BRCA2 germline mutation status.

268 ee had IHC staining patterns consistent with germline mutation status.

269 CK8 deficiency, only certain combinations of germline mutations supported secondary somatic repair.

270 trigger consideration for genetic counseling/germline mutation testing and may serve as a useful cuto

271 how age of onset could indicate the need for germline mutation testing for detection of inherited for

272 idelines exist for patient selection for RCC germline mutation testing.

273 We identified a FEN1 germline mutation that changed residue E359 to K in a pa

274 wever, here we describe for the first time a germline mutation that leads to familial thrombocytosis

275 so featured GATA4 loss of function via GATA4 germline mutations that abrogated GATA4 interactions wit

276 of patient cases of CRC are associated with germline mutations that confer an inherited predispositi

277 h syndrome is caused by dominantly inherited germline mutations that predispose individuals to colore

278 In inherited PD, PARK genes harbor germline mutations; the same genes are somatically mutat

279 multiple renal tumors, each of whom had the germline mutation TSC2 p.R905Q.

280 A germline mutation was identified in 23 probands (53.5 +/

281 ly effective because the overall estimate of germline mutations was 17.3 of 245 patient cases (7.1%;

282 ifferentiation of somatic patient cells with germline mutations was a viable approach to generate LAM

283 Testing for CDH1 germline mutations was performed on 183 index cases meet

284 e and model the pathogenicity of these CDK10 germline mutations, we generated conditional-knockout mi

285 Deleterious germline mutations were also found in BUB1B (1) and BUB3

286 Moreover, many tumors harboring BAP1 germline mutations were associated with BAP1 syndrome, i

287 Deleterious germline mutations were identified in 32 (3.6%) patients

288 horts, and somatic as well as novel and rare germline mutations were identified in 8 and 5% of analyz

289 LZTR1 germline mutations were identified in seven of the eight

290 s in 29 B cell lymphoma samples, somatic and germline mutations were identified in various DNA repair

291 Pathogenic BRCA1 and BRCA2 germline mutations were present in 50 of the 291 patient

292 Germline mutations were present in 50% of children.

293 Patients with these germline mutations were younger than those without (mean

294 ssociated malignancies and were assessed for germline mutations when found to have MBAITs on dermatol

295 The remaining cases with germline mutations, which were predominantly missense mu

296 ing was performed using primers that flanked germline mutations, whose design did not rely on prior k

297 ed 17 of 34 DOCK8-deficient patients who had germline mutations with variable degrees of reversion ca

298 While many germline mutations within microRNAs (miRNAs) and their t

299 to determine a potential association of LoF germline mutations within the FANCM gene with BC and/or

300 and integrates these somatic mutations with germline mutations within the same target sites, genome-