ライフサイエンスコーパス: microsatellite instability

1 o upstream Wnt inhibitors in cancers without microsatellite instability.

2 DNA repair genes that are further linked to microsatellite instability.

3 of genes have been identified in tumors with microsatellite instability.

4 rs for DNA mismatch repair deficiency and/or microsatellite instability.

5 ated with a loss of mismatch repair genes or microsatellite instability.

6 or without prior endoscopy to have CIMP and microsatellite instability.

7 BTB2; these were validated in 86 tumors with microsatellite instability.

8 ons and neoantigenic peptides as a result of microsatellite instability.

9 d molecular features, which include moderate microsatellite instability.

10 es such as the identification of tumors with microsatellite instability.

11 sults in hereditary cancers characterized by microsatellite instability.

12 Gialpha2-/- cancers have microsatellite instability.

13 ity, but not in cells from colon tumors with microsatellite instability.

14 we analysed colon cancer cell lines showing microsatellite instability.

15 ancer and to tumor characteristics including microsatellite instability.

16 een described in numerous cancers exhibiting microsatellite instability.

17 neoplasia, showing monoclonal expansion and microsatellite instability.

18 the more complex strategy of genotyping for microsatellite instability.

19 t in tumours from multiple cancer types with microsatellite instability.

20 sensitivity, HPV status, tumour hypoxia, and microsatellite instability.

21 ivolumab) for the treatment of patients with microsatellite instability.

22 damage, increased mutability, and triggered microsatellite instability.

23 and multiplex polymerase chain reaction for microsatellite instability.

24 h has been associated with BRAF mutation and microsatellite instability.

25 ts those genetic alterations contributing to microsatellite instability.

26 ted in 18% (13 of 78) of CRC tissues without microsatellite instability.

27 MMR-positive patients with tumors exhibiting microsatellite instability (0.121); the difference was n

28 -negative patients with tumors exhibiting no microsatellite instability (0.211), and the lowest frequ

29 dine dehydrogenase, thymidine phosphorylase, microsatellite instability, 18q loss of heterozygosity,

30 BB2/HER2 point mutations (8.2% [26 of 317]), microsatellite instability (7.6% [13 of 170]), and high

31 y event in the normal human aging process is microsatellite instability accumulation in normal human

32 Genotyping for microsatellite instability alone and immunohistochemical

33 the very high frequency of lung cancers with microsatellite instability among chromate workers.

34 he tumor characteristics of all 455 cases by microsatellite instability analysis, in addition to a pa

35 mmunohistochemistry of MLH1, MSH2, and MSH6; microsatellite instability analysis; and hypermethylatio

36 2% (37 of 116) of the colorectal tumors with microsatellite instability analyzed, and evidence of pro

37 MLH1 silencing results in microsatellite instability and a hypermutable phenotype.

38 e oncogene for human colorectal cancers with microsatellite instability and as a predictive indicator

39 pylori status, tumor site, patient survival, microsatellite instability and BRAF and KRAS mutations.

40 donors > 45 years had a greater frequency of microsatellite instability and CD34(+) progenitors lacki

41 hat have been identified in colon cancer are microsatellite instability and chromosome instability.

42 eviously demonstrated an association between microsatellite instability and decreased CDK2-AP1 (p12(D

43 consenting probands and families, including microsatellite instability and DNA mismatch repair immun

44 A high frequency of microsatellite instability and evidence of MSH2 loss in

45 We examined microsatellite instability and expression of the MMR gen

46 tumors from patients with LS were tested for microsatellite instability and immunohistochemistry (IHC

47 atures of the sebaceous neoplasms, including microsatellite instability and immunohistochemistry, wit

48 reatment of patients whose tumours have high microsatellite instability and larotrectinib and entrect

49 Immunohistochemistry and microsatellite instability and MLH1 methylation assays w

50 orrelation of hypermethylated miR-129-2 with microsatellite instability and MLH1 methylation status (

51 Microsatellite instability and MLH1 promoter methylation

52 with low BER/SSBR gene expression show high microsatellite instability and neoantigen production.

53 includes defective DNA mismatch repair with microsatellite instability and POLE mutations in approxi

54 ted DNA polymerases and a distinct impact of microsatellite instability and replication repair defici

55 of consecutive colorectal cancers have high microsatellite instability and that, of this 12%, 25% ha

56 tumoral features, including KRAS, BRAF, p53, microsatellite instability and the CpG island methylatio

57 BRAF V600E mutation has been associated with microsatellite instability and the CpG island methylator

58 CRC) are commonly classified into those with microsatellite instability and those that are microsatel

59 ression levels were strongly associated with microsatellite instability and tumor location in the gas

60 n a tissue-agnostic approach: pembrolizumab [microsatellite instability and tumor mutational burden (

61 SBA cases (91%), and the higher incidence of microsatellite instability and tumor mutational burden i

62 istory, and tumor characteristics, including microsatellite instability and tumor site.

63 given its normal role in protecting against microsatellite instability and while MLH3 does have an a

64 to have tumors with MMR deficiency (based on microsatellite instability and/or absence of MMR protein

65 ch repair (MMR) deficiency was determined by microsatellite instability and/or immunohistochemistry.

66 Tumor testing for microsatellite instability and/or mismatch repair-defici

67 nrolled in the study, 208 (19.5 percent) had microsatellite instability, and 23 of these patients had

68 lignancy; screening of cutaneous lesions for microsatellite instability, and absence of mismatch repa

69 efective DNA repair, chromosome instability, microsatellite instability, and alterations in the serra

70 ade, including high tumor mutational burden, microsatellite instability, and an apolipoprotein B mRNA

71 int inhibitors are used to treat tumors with microsatellite instability, and anti-angiogenic agents m

72 ogenesis: the chromosomal instability (CIN), microsatellite instability, and CpG island methylator ph

73 BRAF- and KRAS-mutation status, microsatellite instability, and CpG island methylator ph

74 lead to sporadic CRC-chromosome instability, microsatellite instability, and DNA hypermethylation-als

75 ave tumor susceptibility, shorter life span, microsatellite instability, and DNA-damage response phen

76 ence (16%, 7 of 43), whereas BRAF wild type, microsatellite instability, and low MACC1 expression def

77 th loss of MSH2 expression, tumors with high microsatellite instability, and lower BMI.

78 of mutations in key regulatory cancer genes, microsatellite instability, and other genes that affect

79 cteristics (CpG island methylator phenotype, microsatellite instability, and the B-Raf protooncogene,

80 is frequently deleted in human tumors due to microsatellite instability-associated mutations.

81 predicts colon cancer molecular subtypes and microsatellite instability based on broad CNA scores and

82 A relapsed leukemia patient displayed microsatellite instability, but no genetic and epigeneti

83 Microsatellite instability can be found in approximately

84 ed human CRC tissues and cell lines that had microsatellite instability contained truncations in the

85 py, including tumor mutational burden (e.g., microsatellite instability), copy-number alterations, an

86 Neither PTEN loss nor microsatellite instability correlated with efficacy.

87 n tumor molecular characteristics (including microsatellite instability, CpG island methylator phenot

88 uding PTGS2, phosphorylated AKT, KRAS, BRAF, microsatellite instability, CpG island methylator phenot

89 g for clinical and tumor features, including microsatellite instability, CpG island methylator phenot

90 hort, two of which overlapped with the TCGA 'microsatellite instability/CpG island methylation phenot

91 approximately 20% that overlap greatly with microsatellite instability CRCs and some nonhypermutated

92 Microsatellite instability determines whether patients w

93 mutations and molecular pathways, including microsatellite instability, epigenetics, microbiota, and

94 data were combined, providing rationale for microsatellite instability for 8 of the 9 cell lines in

95 uding loss of the INK4a tumor suppressor and microsatellite instability from reduction of the DNA mis

96 on with a concrete example that involves the microsatellite instability gene MLH1.

97 Microsatellite instability had been determined previousl

98 However, the presence or absence of microsatellite instability has a major effect on the exp

99 The role of microsatellite instability has been a subject of discuss

100 herapy, and mismatch repair gene defects and microsatellite instability have been associated with res

101 T1 mRNA was not translated in CRC cells with microsatellite instability (HCT116).

102 oss of MMR protein expression (MMR-D) and/or microsatellite instability high (MSI-H) genotype.

103 Although sporadic microsatellite instability high tumors had the highest a

104 dations for germline and somatic testing for microsatellite instability high/mismatch repair deficien

105 e (WRN) as a novel specific vulnerability of microsatellite instability-high (MSI-H) cancer cells.

106 astatic DNA mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cance

107 hypermethylation status of MLH1 (MLH1ph) in microsatellite instability-high (MSI-H) colorectal carci

108 Microsatellite instability-high (MSI-H) tumors are chara

109 In patients with microsatellite instability-high (MSI-H) tumors, longer O

110 ell infiltration and increased glycolysis in microsatellite instability-high (MSI-H) tumors, suggesti

111 tivity of pembrolizumab in Hodgkin lymphoma, microsatellite instability-high tumours, and melanoma.

112 by the associations of CIMP-high cancer with microsatellite instability-high, DNMT3B-positive, and BR

113 between CGI methylation and hypermutability, microsatellite instability, IDH1 mutation, 19p gain and

114 s (CMSs) with distinguishing features: CMS1 (microsatellite instability immune, 14%), hypermutated, m

115 Mlh3 deficiency alone causes microsatellite instability, impaired DNA-damage response

116 ents, mutations of BRAF in 15% patients, and microsatellite instability in 26% patients.

117 ic SETD2 aberrations are not associated with microsatellite instability in ccRCC.

118 Microsatellite instability in colorectal cancer predicts

119 subject of discussion, and data suggest that microsatellite instability in inflammatory bowel disease

120 eover, although bulk analyses did not detect microsatellite instability in MMR-deficient gliomas, sin

121 ng repeat sequences: DNMT1 deficiency causes microsatellite instability in mouse embryonic stem cells

122 is revealed that Immunoscore was superior to microsatellite instability in predicting patients' disea

123 matory bowel disease might be different from microsatellite instability in sporadic colorectal cancer

124 (EXO1, MSH2, and MSH6) were associated with microsatellite instability, increased number of somatic

125 Microsatellite instability is associated with 10% to 15%

126 While microsatellite instability is implicated in numerous gen

127 immunotherapy, mismatch-repair-proficient or microsatellite instability-low (pMMR-MSI-L) tumors have

128 stage II disease, molecular markers such as microsatellite instability might help select patients fo

129 Microsatellite instability (MIN) leads to by elevated po

130 ay MSI or abnormal IHC (often referred to as microsatellite instability [MIN] pathway).

131 non-polyposis colon cancer, Lynch syndrome, microsatellite instability, mismatch repair genes, and t

132 athology testings (for example, analyses for microsatellite instability, MLH1 promoter CpG island met

133 Microsatellite instability, MLH1 promoter hypermethylati

134 Most tumors showed microsatellite instability, more marked at dinucleotide

135 Case tissue samples were obtained for microsatellite instability (MSI) analyses.

136 l as from adjacent normal control tissue and microsatellite instability (MSI) analysis using 5 highly

137 ridization (aCGH), mutational profiling, and microsatellite instability (MSI) analysis.

138 Colorectal cancers (CRCs) with microsatellite instability (MSI) and a mismatch repair (

139 the H3K36 trimethyltransferase SETD2 display microsatellite instability (MSI) and an elevated spontan

140 MP1) is a distinct phenotype associated with microsatellite instability (MSI) and BRAF mutation in co

141 Two major classes of genetic instability, microsatellite instability (MSI) and chromosome instabil

142 We characterized 100 sporadic CRCs for microsatellite instability (MSI) and CIN.

143 s have investigated the relationship between microsatellite instability (MSI) and colorectal cancer (

144 These cancers exhibit hypermutability with microsatellite instability (MSI) and differ from microsa

145 iffers by the molecular pathologic status of microsatellite instability (MSI) and expression of cell-

146 here tumors were available were screened for microsatellite instability (MSI) and expression of MSH2

147 In a subset of patients, we assessed microsatellite instability (MSI) and expression of the m

148 Microsatellite instability (MSI) and genomic hypermethyl

149 Microsatellite instability (MSI) and mismatch-repair def

150 Most studies of microsatellite instability (MSI) and outcomes in endomet

151 te that genomic instability, as evidenced by microsatellite instability (MSI) and promoter methylatio

152 Heterogeneity for microsatellite instability (MSI) and promoter methylatio

153 r depletion of MutSalpha from cells leads to microsatellite instability (MSI) and resistance to DNA d

154 The relationship between microsatellite instability (MSI) and response to neoadju

155 clinical evidence showing that the degree of microsatellite instability (MSI) and resultant mutationa

156 Microsatellite instability (MSI) and/or mismatch repair

157 Colorectal cancers (CRCs) displaying DNA microsatellite instability (MSI) are associated with a f

158 Tumors with microsatellite instability (MSI) are caused by a defecti

159 Mismatch repair (MMR) deficiency (MMRD) and microsatellite instability (MSI) are prognostic for surv

160 MSH2, MSH6, and PMS2 protein expression and microsatellite instability (MSI) are well-established to

161 for loss of heterozygosity at BMPR2 and for microsatellite instability (MSI) at 5 loci.

162 onger disease-free survival in patients with microsatellite instability (MSI) cancers, but no such co

163 Microsatellite instability (MSI) caused by mismatch repa

164 These were found in microsatellite instability (MSI) cell lines and 43% of M

165 Patients with colorectal tumors with microsatellite instability (MSI) have better prognoses t

166 Colorectal cancers (CRC) with microsatellite instability (MSI) have clinical, patholog

167 nal spectrum, and functional consequences of microsatellite instability (MSI) in cancer genomes.

168 S. cerevisiae and also induced high rates of microsatellite instability (MSI) in human cells.

169 ting the prognostic and predictive impact of microsatellite instability (MSI) in human colon carcinom

170 Microsatellite instability (MSI) is a clonal change in t

171 Microsatellite instability (MSI) is a hallmark of cancer

172 Microsatellite instability (MSI) is a hallmark of mismat

173 Microsatellite instability (MSI) is a hypermutable pheno

174 Microsatellite instability (MSI) is a molecular phenotyp

175 Microsatellite instability (MSI) is an important indicat

176 Microsatellite instability (MSI) is displayed by approxi

177 umulation of DNA replication errors known as microsatellite instability (MSI) is the hallmark lesion

178 specific mutations in DDR genes and elevated microsatellite instability (MSI) levels support the impo

179 ctal cancers (CRCs) are classified as having microsatellite instability (MSI) or chromosomal instabil

180 be screened for Lynch syndrome (LS) through microsatellite instability (MSI) or immunohistochemistry

181 However, it is unclear whether microsatellite instability (MSI) or immunohistochemistry

182 median [range] age, 60.0 [19.0-75.0] years), microsatellite instability (MSI) phenotype, KRAS, and BR

183 Microsatellite instability (MSI) refers to the hypermuta

184 Colorectal cancers with microsatellite instability (MSI) represent 15% of all co

185 analysis identified a cancer cell-intrinsic microsatellite instability (MSI) signature, which was ef

186 ation series lack complete information about microsatellite instability (MSI) status and pathology as

187 Tumor mutation burden (TMB) and microsatellite instability (MSI) status were also assess

188 All tumors underwent microsatellite instability (MSI) testing.

189 myelodysplastic syndrome (MDS) exhibited the microsatellite instability (MSI) that is diagnostic for

190 ffective in selecting for cells with reduced microsatellite instability (MSI) that is inherent in mis

191 We sought to determine whether tumor microsatellite instability (MSI) typing along with immun

192 or and plasma MGMT promoter methylation, and microsatellite instability (MSI) were examined in 14 of

193 eling family, in 83% of gastric cancers with microsatellite instability (MSI), 73% of those with Epst

194 ynthetic lethal target for cancer cells with microsatellite instability (MSI), a form of genetic hype

195 ed UVRAG(FS) in colorectal cancer (CRC) with microsatellite instability (MSI), and promotes tumorigen

196 s were analyzed for the presence of fusions, microsatellite instability (MSI), and RAS/BRAF mutations

197 rs underwent MMR immunohistochemistry (IHC), microsatellite instability (MSI), and targeted MLH1-meth

198 , p21, beta-catenin, LINE-1 hypomethylation, microsatellite instability (MSI), and the CpG island met

199 (CRC) cell lines and in primary tumors with microsatellite instability (MSI), but not in microsatell

200 heterogeneous disease, with factors such as microsatellite instability (MSI), cancer subsite within

201 omic instability are common in colon cancer: microsatellite instability (MSI), chromosome instability

202 All the studies collected information on microsatellite instability (MSI), CpG island methylator

203 proposed, based on specific combinations of microsatellite instability (MSI), CpG island methylator

204 ding 9,592 cases with molecular subtypes for microsatellite instability (MSI), CpG island methylator

205 RC by major molecular pathological features: microsatellite instability (MSI), CpG island methylator

206 s are resistant to genotoxic agents and have microsatellite instability (MSI), due to accumulation of

207 omarkers, including major mutational events, microsatellite instability (MSI), epigenetic features, p

208 d the cases of 32 NADC patients, focusing on microsatellite instability (MSI), genetic mutations, CpG

209 We also looked for microsatellite instability (MSI), germline mutations in

210 lly clinically relevant genotypes, including microsatellite instability (MSI), homologous recombinati

211 luding the CpG island methylation phenotype, microsatellite instability (MSI), LINE-1 hypomethylation

212 from NRG/GOG0210 patients were assessed for microsatellite instability (MSI), MLH1 methylation, and

213 ociation with tumor mutational burden (TMB), microsatellite instability (MSI), programmed cell death

214 r mechanisms in colorectal cancer (CRC) with microsatellite instability (MSI), somatic mutations accu

215 Microsatellite instability (MSI), the spontaneous loss o

216 smatch repair plays a key role in preventing microsatellite instability (MSI), which is a hallmark of

217 roximately 15% of colorectal cancers exhibit microsatellite instability (MSI), which leads to accumul

218 Microsatellite instability (MSI), which occurs in 15% of

219 ips, we queried dependencies in cancers with microsatellite instability (MSI), which results from def

220 was 63.6% (30.8% to 89.1%) in patients with microsatellite instability (MSI)-high tumors (n = 11) an

221 of recurrent indels that may serve to detect microsatellite instability (MSI).

222 Tumors are characterized by microsatellite instability (MSI).

223 cers have mismatch repair gene mutations and microsatellite instability (MSI).

224 sor Bax is frequently mutated in tumors with microsatellite instability (MSI).

225 ions that define this syndrome and result in microsatellite instability (MSI).

226 development and is inversely associated with microsatellite instability (MSI).

227 ct classes: chromosome instability (CIN) and microsatellite instability (MSI).

228 They die of invasive GI tumors that display microsatellite instability (MSI).

229 mined these associations stratified by tumor microsatellite instability (MSI).

230 mismatch repair genes and hence demonstrate microsatellite instability (MSI).

231 ctive DNA mismatch repair (MMR) indicated by microsatellite instability (MSI).

232 cular manifestation of this repair defect is microsatellite instability (MSI).

233 3, MGMT, MINT1, MINT31, p14 [ARF], and WRN); microsatellite instability (MSI); the CpG island methyla

234 otype), including simple repeat instability [microsatellite instability (MSI)] are a signature of MMR

235 ectal cancer (CRC) cells with high levels of microsatellite instability (MSI-H) accumulate mutations

236 ght to determine the frequency of high-level microsatellite instability (MSI-H) and the mutational an

237 The role of high-degree microsatellite instability (MSI-H) as a marker to predic

238 Colon cancers with high-frequency microsatellite instability (MSI-H) develop frameshift mu

239 The high microsatellite instability (MSI-H) is frequently observe

240 with colon cancer who demonstrate high-level microsatellite instability (MSI-H) or defective DNA mism

241 CIMP is probably the cause of high-frequency microsatellite instability (MSI-H) sporadic CRCs, its ro

242 equently occurred in colon cancers with high microsatellite instability (MSI-H).

243 l cancer cells frequently have low levels of microsatellite instability (MSI-L) and elevated microsat

244 ensity was significantly higher in low-level microsatellite instability (MSI-L) than in non-MSI-L can

245 yzed by direct sequencing in 141 tumors with microsatellite instability (MSI-positive) and 107 micros

246 al/family history of cancer or polyps, tumor microsatellite instability [MSI], mismatch repair [MMR]

247 ed on combinations of tumor markers: type 1 (microsatellite instability [MSI]-high, CpG island methyl

248 odds ratio, 2.19; 95% CI, 1.14 to 4.21) and microsatellite instability (multivariate odds ratio, 2.1

249 ns and inference of tumor mutational burden, microsatellite instability, mutational signatures and so

250 al cancer biomarkers and are associated with microsatellite instability, namely MLH1, PMS2, MSH2, MSH

251 d from chromosomal instability neoplasia and microsatellite instability neoplasia CRC subtypes and to

252 Some colorectal and endometrial tumors with microsatellite instability not attributable to MLH1 hype

253 e previously shown that distinct patterns of microsatellite instability occur in upper and lower urin

254 individuals' tumor tissue demonstrated high microsatellite instability of di- and tetranucleotides (

255 (HR: 1.99; 95% CI: 1.10, 3.56) but not with microsatellite instability or CpG island methylator phen

256 ) CRIS-A: mucinous, glycolytic, enriched for microsatellite instability or KRAS mutations; (ii) CRIS-

257 etastatic endometrial cancer (unselected for microsatellite instability or PD-L1), had an Eastern Coo

258 independent of tumor staging, site location, microsatellite instability or stability, and patient tre

259 chromosomal gains or losses, a high level of microsatellite instability, or the presence of Helicobac

260 by age at diagnosis, family history of CRC, microsatellite instability, or tumor site at either locu

261 ance of oncogenic BRAF mutation coupled with microsatellite instability, p16Ink4a inactivation, and p

262 me-wide copy-number variation and a moderate microsatellite instability phenotype compared with Msh2/

263 etween smoking cessation and cancer risks by microsatellite instability (Pheterogeneity = 0.02), DNMT

264 In a panel of 40 samples from microsatellite instability-positive colon cancer patient

265 lopment and clinical behavior of a subset of microsatellite instability-positive endometrial, colon,

266 r contributing to phenotypic variation among microsatellite instability-positive tumors.

267 Archival tissues were analyzed for microsatellite instability, PTEN status, and 487-gene se

268 eatures and is responsible for most cases of microsatellite instability related to hMLH1 inactivation

269 several gene signatures representing HPV and microsatellite instability remained significant in multi

270 ignatures for radiosensitivity, hypoxia, and microsatellite instability revealed significant underlyi

271 Except for tumor samples with microsatellite instability, RNAIndel robustly predicts 8

272 nal effects of mutations at other regions of microsatellite instability should be evaluated.

273 potent indicator of tumor recurrence beyond microsatellite-instability staging that could be an impo

274 MIRMMR predicts microsatellite instability status in cancer samples usin

275 Tumor microsatellite instability status was available for 95 p

276 on (right sided), poor differentiation, high microsatellite instability status, and a positive first-

277 canonical CIMP-related loci and 7 new loci), microsatellite instability status, and BRAF/KRAS mutatio

278 with the tumor's clinicopathologic details, microsatellite instability status, and subsequent behavi

279 Fresh-frozen tissue, microsatellite instability status, clinical parameters,

280 Patterns of concurrent mutations, microsatellite instability status, CpG island methylatio

281 2, TP53, CpG island methylator phenotype, or microsatellite instability status.

282 umor's progression stage, origin, and likely microsatellite instability status.

283 gene expression that correlated with patient microsatellite instability status.

284 in these double somatic tumors than in other microsatellite-instability subgroups.

285 In stage II disease, for example, microsatellite instability supports observation after su

286 protein loss, supported by BRAF mutation and microsatellite instability testing.

287 For HNPCC, 80%-95% can be identified by microsatellite instability testing.

288 In recurrent disease, the absence of microsatellite instability (the standard marker for MMR

289 d ratio (HR); calculations were adjusted for microsatellite instability; the CpG island methylator ph

290 icrosatellite-stable tumors from tumors with microsatellite instability, thus potentially improving c

291 for clinical and tumoral features, including microsatellite instability, TP53 (p53), PTGS2 (cyclooxyg

292 ated, and family characteristics, as well as microsatellite instability, tumor MMR immunostaining, an

293 owever, the mechanistic relationship between microsatellite instability, tumor-infiltrating immune ce

294 s of CpG island methylator phenotype (CIMP), microsatellite instability, v-raf murine sarcoma viral o

295 DNA microsatellite instability was also assessed using a pan

296 Recruitment of patients with high microsatellite instability was capped at 5%.

297 Microsatellite instability was independently associated

298 Microsatellite instability was observed in all VCMsh2 st

299 Genotyping of the tumor for microsatellite instability was the primary screening met

300 ts whose screening results were positive for microsatellite instability, we searched for germ-line mu