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1.
Cyclin D1 is overexpressed in atypical teratoid/rhabdoid tumor with <Emphasis Type="Italic">hSNF5/INI1</Emphasis> gene inactivation 总被引:2,自引:0,他引:2
Fujisawa H Misaki K Takabatake Y Hasegawa M Yamashita J 《Journal of neuro-oncology》2005,73(2):117-124
Object: Although atypical teratoid/rhabdoid tumor (AT/RT) is known to generate through inactivation of the hSNF5/INI1 gene on chromosome 22q, the downstream molecular mechanism remains unclear. We histologically and molecularly reviewed our pediatric brain tumors for unrecognized AT/RTs and evaluated the role of cyclin D1, a potential molecular target of hSNF5/INI1. Methods: We analyzed 16 tumors under three years of age: seven medulloblastomas, three anaplastic ependymomas (E IIIs), two each of supratentorial primitive neuroectodermal tumors (sPNETs) and choroid plexus carcinomas (CPCs), and one each of neuroblastoma and pineoblastoma. Immunohistochemistry for glial fibrillary acidic protein, vimentin, epithelial membrane antigen, smooth muscle actin and cyclin D1 was performed. Polymerase chain reaction (PCR)-single-strand conformation polymorphism analysis with direct sequencing, differential PCR and microsatellite analysis were conducted for hSNF5/INI1mutation, homozygous deletion and loss of heterozygosity (LOH) on 22q, respectively. Because of the presence of rhabdoid cells and the polyimmunophenotypic features, the diagnosis was revised to AT/RT in five (31%) tumors, namely, two E IIIs and one each of medulloblastoma, CPC and pineoblastoma. Three of them harbored such hSNF5/INI1 aberrations as germline single base deletion (492/6 delC) and missense mutation (C157T) together with LOH 22q or homozygous deletion. Cyclin D1 was overexpressed in those three tumors but not in the two that lacked hSNF5/INI1 inactivation. Conclusion: AT/RT can be misdiagnosed as a variety of tumors, including ependymoma that potentially harbors LOH 22q. Our data indicate that cyclin D1 is a target of hSNF5/INI1in primary tumors. 相似文献
2.
Ammerlaan AC Ararou A Houben MP Baas F Tijssen CC Teepen JL Wesseling P Hulsebos TJ 《British journal of cancer》2008,98(2):474-479
Rhabdoid tumour predisposition syndrome (RTPS) is a rare syndrome caused by inheritance of a mutated INI1 gene for which only two multigeneration families have been reported. To further characterise the genotype and phenotype of RTPS, we present a third family in which at least three cousins developed an atypical teratoid/rhabdoid tumour (AT/RT) at a young age. Two of these patients showed unusual long survival, and one of these developed an intracranial meningioma and a myoepithelioma of the lip in adulthood. Mutation analysis of INI1 revealed a germline G>A mutation in the donor splice site of exon 4 (c.500+1G>A) in the patients and in their unaffected fathers. This mutation prevents normal splicing and concomitantly generates a stop codon, resulting in nonsense-mediated mRNA decay. Biallelic inactivation of INI1 in the tumours, except for the meningioma, was confirmed by absence of nuclear INI1-protein staining. The myoepithelioma of one of the patients carried an identical somatic rearrangement in the NF2 gene as the AT/RT, indicating that both tumours originated from a common precursor cell. In conclusion, this study demonstrates for the first time transmission of a germline INI1-mutation in a RTPS family via nonpenetrant males, long-term survival of two members of this family with an AT/RT, and involvement of INI1 in the pathogenesis of myoepithelioma. 相似文献
3.
Makuria AT Rushing EJ McGrail KM Hartmann DP Azumi N Ozdemirli M 《Journal of neuro-oncology》2008,88(3):321-330
Atypical teratoid/rhabdoid (AT/RT) tumor is a rare, highly malignant tumor of the central nervous system (CNS) most commonly found in children less than 5 years of age. Although the vast majority of cases are diagnosed in young children, there have been isolated case reports in adults. Since its histological appearance can be confused with other tumors, especially in adults, separating AT/RT from other neoplasms may be difficult. In many instances, a reliable diagnosis is not possible without demonstrating the lack of nuclear INI1 protein expression by immunohistochemical methods. The patients (three males and one female) ranged in age from 23 to 42 years (mean age, 32 years). Radiographically, two tumors were localized in the right fronto-parietal region, one was frontal and the other was found in the left temporal lobe. Varying degrees of hydrocephalus and heterogeneous enhancement were present on MRI. In all cases, diagnosis during intraoperative consultation and preliminary diagnosis was different from the final diagnosis after immunohistochemical analysis. Immunohistochemical staining showed that the tumor cells were positive for vimentin and reacted variably for keratin, epithelial membrane antigen (EMA), synaptophysin, neurofilament protein, CD34, and smooth muscle actin (SMA). All were negative for GFAP, S-100, desmin and CD99. Three of the four cases lacked nuclear expression of INI1. One patient is alive with no evidence of disease 17 years after the diagnosis. In adult examples of AT/RT, the diagnosis requires a high index of suspicion, with early tissue diagnosis and a low threshold for investigation with INI1 immunohistochemistry to differentiate this entity from other morphologically similar tumors. Although the prognosis is dismal in pediatric population, long term survival is possible in adult AT/RT cases after surgery and adjuvant radiotherapy and chemotherapy. 相似文献
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SMARCB1/INI1 is one of the core subunit proteins of the ATP‐dependent SWI/SNF chromatin remodeling complex, and is identified as a potent and bona fide tumor suppressor. Interactions have been demonstrated between SMARCB1/INI1 and key proteins in various pathways related to tumor proliferation and progression: the p16‐RB pathway, WNT signaling pathway, sonic hedgehog signaling pathway and Polycomb pathway. Initially, no detectable SMARCB1/INI1 protein expression was found in malignant rhabdoid tumor cells, whereas all other kinds of tumor cells and non‐tumorous tissue showed SMARCB1/INI1 protein expression. Therefore, immunohistochemical testing for the SMARCB1/INI1 antibody has been considered useful in confirming the histologic diagnosis of malignant rhabdoid tumors. However, recently, aberrant expression of SMARCB1/INI1 has been found in various tumors such as epithelioid sarcomas, schwannomatosis, synovial sarcomas, and so on. In addition, it has been reported that aberrant expression can be classified into three patterns: complete loss, mosaic expression and reduced expression. Although the various pathways related to mechanisms of tumorigenesis and tumor proliferation are complexly intertwined, the clarification of these mechanisms may contribute to therapeutic strategies in SMARCB1/INI1‐deficient tumors. In terms of pathological classifications, SMARCB1/INI1‐deficient tumors may be re‐classified by genetic backgrounds. 相似文献
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Zarovnaya EL Pallatroni HF Hug EB Ball PA Cromwell LD Pipas JM Fadul CE Meyer LP Park JP Biegel JA Perry A Rhodes CH 《Journal of neuro-oncology》2007,84(1):49-55
Atypical teratoid/rhabdoid tumors (AT/RTs) are rare, malignant brain tumors which occur almost exclusively in infants and
young children. There have been only 17 cases of AT/RT in adults reported in the medical literature and the rarity of this
tumor makes the diagnosis in adults difficult. We describe a case of an AT/RT of the spinal cord in an adult. A 43-year old
woman presented with neck and left upper extremity pain. An MRI demonstrated a mass lesion in the dorsal spinal cord extending
from C4 to C6. The patient underwent a C3 through C7 laminectomy. In consultation with senior pathologists at other institutions,
the lesion was initially diagnosed as a rhabdoid meningioma. Molecular genetic studies revealed monosomy 22 and loss of expression
of the INI1 gene in 22q11.2. Subsequently, immunohistochemical studies revealed the absence of INI1 gene expression in the
malignant cells, supporting the diagnosis of AT/RT. The patient underwent three additional surgical procedures for recurrent
disease throughout the neuraxis secondary to leptomeningeal spread of the tumor. Despite aggressive surgical resection, adjuvant
chemotherapy and radiation therapy, the patient succumbed to the disease two and a half years after her initial presentation.
An unrestricted autopsy was performed. To our knowledge, this is the first case of a spinal atypical teratoid/rhabdoid tumor
in an adult fully documented with molecular, immunohistochemical, cytogenetic and autopsy findings. 相似文献
8.
Lutterbach Johannes Liegibel Jürgen Koch Donatus Madlinger Albrecht Frommhold Hermann Pagenstecher Axel 《Journal of neuro-oncology》2001,52(1):49-56
Atypical teratoid/rhabdoid tumors (AT/RT) of the central nervous system are rare and extremely aggressive malignancies of early childhood. We report a case of AT/RT in an adult patient.A 30-year-old woman presented with headache, vomiting and ataxia during the second trimester of pregnancy. Magnetic resonance imaging revealed a posterior fossa mass. A gross total resection was performed. Pathological examination revealed an AT/RT. Despite the dismal prognosis the patient decided not to undergo an abortion. For this reason postoperative accelerated hyperfractionated radiotherapy was limited to the tumor region. Six months later the woman delivered a healthy baby. One week postpartum, a central nervous system recurrence localized apart from the primary lesion was treated with radiosurgery. Two months later a diffuse progression was noted. Despite a 6 week course of oral temozolomide, the tumor progressed and the patient died 11 months after diagnosis.Although survival was short, surgery and involved field radiotherapy yielded a progression-free interval of 9 months. This allowed the patient to carry pregnancy to term. Radiosurgery resulted in a complete remission of the first recurrence. Oral chemotherapy was not effective in controlling diffuse tumor spread. 相似文献
9.
Erickson ML Johnson R Bannykh SI de Lotbiniere A Kim JH 《Journal of neuro-oncology》2005,74(3):311-319
Summary Rhabdoid tumors of the central nervous system are uncommon, aggressive childhood malignancies. The 13 described adult cases
comprise both primary CNS tumors and malignant transformation of previously existing gliomas, meningiomas, and astrocytomas.
Central nervous system rhabdoid lesions of adults have been diagnosed as primary malignant rhabdoid tumors, atypical teratoid/rhabdoid
tumors, and more recently, rhabdoid glioblastomas. We report a case of a 20-year-old woman in her 30th week of pregnancy who
presented with headache, nausea and blurry vision. MRI revealed a large rim-enhancing mass of the right occipital lobe. Gross
total resection was achieved via a right parietal-occipital craniotomy. Pathologic evaluation revealed histology, electron
microscopy and immunohistochemistry consistent with the diagnosis of malignant rhabdoid tumor. FISH studies were negative
for the INI-1 genetic mutations and chromosome 22q deletion associated with childhood atypical rhabdoid/rhabdoid tumor in 75% of cases.
The patient delivered her infant via caesarian section prior to initiating further therapy. We briefly describe the characteristics
and current understanding of rhabdoid tumors, and review the literature comparing the 12 other cases of central nervous system
rhabdoid tumors in adults. Furthermore, we consider and discuss the implications of this case being the second presentation
of MRT during pregnancy in only six adult female patients. 相似文献
10.
Atypical Teratoid/ Rhabdoid Tumor of Brain: a Clinicopathologic Study of Eleven Patients and Review of Literature
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Nasir Ud DinAbrar BarakzaiAisha MemonSheema HasanZubair Ahmad 《Asian Pacific journal of cancer prevention》2017,18(4):949-954
Background: Atypical teratoid/ rhabdoid tumor (AT/RT) is a rare aggressive embryonal central nervous system(CNS) tumor of infancy and early childhood. Majority of the cases arise in the posterior fossa, and remaining in thecerebrum. Aims: To analyze the clinicopathologic features of AT/RT on a cohort of cases. Materials and methods:All reported cases of AT/RT at the Department of Pathology and Laboratory Medicine, Aga Khan University Hospital(AKUH) from 2007 to 2016 were reviewed for clinical and pathological features. Immunohistochemical stain for INI-1was performed in all 11 cases. Follow up was obtained. Results: A total of 11 cases were identified. Seven patients weremales and 4 were females. The ages ranged from 1 month to 48 months (mean 26.6 months). Six tumors were locatedin the cerebrum and 3 in the posterior fossa. Exact Location was not known in 2 cases. Histologically, rhabdoid cellswere present in sheets in variable proportions in five cases, Medulloblastoma and PNET like areas were seen in 2 caseseach. Immunohistochemical stains EMA (10/10), vimentin (7/7), CKAE1/AE3 (8/9), and CD99 (3/4), GFAP (6/10),ASMA (3/4) and synaptophysin (3/4) were positive in varying proportions while desmin was negative in all 6 cases inwhich it was performed. All 11 tumors lacked immunoreactivity for INI-1 protein. Four patients died of disease witha follow up ranging from 5 to 24 months. Conclusions: AT/RT is a rare highly aggressive embryonal tumor of CNS.A male predominance was noted in our series. We report the first and largest series from Pakistan. 相似文献
11.
Buslov KG Iyevleva AG Chekmariova EV Suspitsin EN Togo AV Kuligina ESh Sokolenko AP Matsko DE Turkevich EA Lazareva YR Chagunava OL Bit-Sava EM Semiglazov VF Devilee P Cornelisse C Hanson KP Imyanitov EN 《International journal of cancer. Journal international du cancer》2005,114(4):585-589
The gene for Nijmegen chromosomal breakage syndrome (NBS1) plays a role in a variety of processes protecting chromosomal stability. Recently, it was suggested in a Polish case-control study that the founder hypomorphic mutation in NBS1, 657del5, which occurs in approximately 0.5% of Slavic subjects, may be associated with an increased risk of breast cancer (BC). We attempted to validate these findings in Russian subjects, who are also of Slavic descent. Heterozygous carriers for the 657del5 mutation were detected in 2 of 173 (1.16%) bilateral breast cancer cases, 5 of 700 (0.71%) unilateral breast cancer patients, 2 of 348 (0.57%) healthy middle-aged females and in 0 of 344 elderly tumor-free women. The difference between the "extreme" cohorts, i.e., biBC patients vs. elderly controls, approached the formal limit of statistic significance (p=0.046). LOH at NBS1 was detected in only 3 of 5 available breast tumors from NBS1 657del5-carriers. In 2 of these tumors, the loss involved the mutant NBS1-allele. Overall, our data suggest that the NBS1 657del5 allele may contribute only to a limited fraction of breast cancer cases in Russia. 相似文献
12.
Paola Fidani Maria Antonietta De Ioris Annalisa Serra Luigi De Sio Ilaria Ilari Raffaele Cozza Renata Boldrini Giuseppe Maria Milano Maria Luisa Garrè Alberto Donfrancesco 《Journal of neuro-oncology》2009,92(2):177-183
Purpose Atypical Teratoid/Rhabdoid Tumour is a rare and aggressive childhood tumour. The outcome of a series treated with the same
multimodal strategy was reported. Patients The patients were treated with surgery, 2 courses of ifosfamide/carboplatin/etoposide(ICE), 2 courses of cyclophosphamide/etoposide/carboplatino/thiotepa
(CECAT) or 2 other ICE courses, high dose chemotherapy (HDC) and radiotherapy. Results Eight patients underwent primary surgery achieving a complete removal in 3. Progressive disease (PD) occurred in 2/8 patients
during ICE courses and in 3/4 during CECAT courses. After 4 courses 5 patients presented a PD. HDC was performed in 3 patients
followed by local radiotherapy. The Kaplan Meier OS and EFS probability at 5 years are, respectively, 50% (CI 11–80%) and
33% (CI 6–66%). Conclusion A strategy based on surgery, including a second surgical look, and on radiotherapy appears the best option. ICE regimen and
HDC correlate with good prognosis in some patients but this approach needs further evaluation. 相似文献
13.
Z Kote-Jarai S Jugurnauth S Mulholland D A Leongamornlert M Guy S Edwards M Tymrakiewitcz L O'Brien A Hall R Wilkinson A A Al Olama J Morrison K Muir D Neal J Donovan F Hamdy D F Easton The UKGPCS Collaborators The British Association of Urological Surgeons' Section of Oncology R Eeles 《British journal of cancer》2009,100(2):426-430
Although prostate cancer (PrCa) is one of the most common cancers in men in Western countries, little is known about the inherited factors that influence PrCa risk. On the basis of the fact that BRIP1/FANCJ interacts with BRCA1 and functions as a regulator of DNA double-strand break repair pathways, and that germline mutations within the BRIP1/FANCJ gene predispose to breast cancer, we chose this gene as a candidate for mutation screening in familial and young-onset PrCa cases. We identified a truncating mutation, R798X, in the BRIP1/FANCJ gene in 4 out of 2714 UK PrCa cases enriched for familial (2 out of 641; 0.3%) and young-onset cases (2 out of 2073; 0.1%). On screening 2045 controls from the UK population, we found one R798X sequence alteration (0.05%; odds ratio 2.4 (95% CI 0.25–23.4)). In addition, using our data from a genome-wide association study, we analysed 25 SNPs in the genomic region of the BRIP1/FANCJ gene. Two SNPs showed evidence of association with familial and young-onset PrCa (rs6504074; Ptrend=0.04 and rs8076727; Ptrend=0.01). These results suggest that truncating mutations in BRIP1/FANCJ might confer an increased risk of PrCa and common SNPs might also contribute to the alteration of risk, but larger case–control series will be required to confirm or refute this association. 相似文献
14.
Izycka-Swieszewska E Debiec-Rychter M Wasag B Wozniak A Gasecki D Plata-Nazar K Bartkowiak J Lasota J Limon J 《Journal of neuro-oncology》2003,64(3):219-225
This report describes the clinical, pathological, immunohistochemical and genetic data of two rare malignant neoplasms of the central nervous system (CNS) – a cerebral atypical teratoid/rhabdoid tumor (AT/RT) in a 5-month-old girl and a spinal canal primitive neuroectodermal tumor (PNET) in her father. Despite aggressive treatment, both tumors were fatal, displaying extensive local recurrence and diffuse neoplastic dissemination. The paraffin-embedded tumor tissue samples were analyzed using a dual-color FISH with a locus specific LSI22q (BCR) probe. In the AT/RT tissue, a loss of BCR locus was observed in a significant proportion of the cells in contrast to the PNET specimen where the majority of nuclei did not reveal any loss of the BCR region. No mutations in exon 5 and no changes in SNP of intron 5 of hSNF/INI1 gene were found. In addition, analysis of loss of heterozygosity (LOH) was performed using a panel of 15 microsatellite markers of chromosome 22. No LOH were found in both tumor tissues. In both cases no constitutional mutations of gene TP53 were found. Analysis of the TP53 mutations in the tumor tissues revealed that the PNET, not the AT/RT tumor, was homozygous for a missense mutation at codon 175 (CGC CAC). Thus, our findings emphasize the genetic differences between the two specimens and suggest that the occurrence of these two aggressive tumors of CNS in one family could be coincidental. 相似文献
15.
Lugtenberg RT Cransberg K Loos WJ Wagner A Alders M van den Heuvel-Eibrink MM 《Cancer chemotherapy and pharmacology》2008,62(6):1039-1044
The therapeutic strategy for bilateral Wilms tumor (WT) remains a challenge. Especially in cases with chemotherapy resistant
disease, bilateral nephrectomy is sometimes inevitable. For optimal cure rates stage V WT patients benefit from adjuvant treatment;
however, there are limited data available on chemotherapy pharmacokinetics in anephric children. In this report, we describe
a 10-month old girl with bilateral Wilms tumor and a novel germline WT1 gene mutation. This patient hardly showed any response on preoperative chemotherapy, and ultimately, underwent sequential
bilateral tumor-nephrectomy. Subsequently, during peritoneal dialysis, she received topotecan as adjuvant chemotherapy based
on plasma levels, indicating that this is a reasonable option as adjuvant treatment in therapy-resistant Wilms tumor patients
after bilateral nephrectomy. This case showed a novel germline WT1 gene mutation of which the correlation with resistant phenotype has to be confirmed in larger cohorts of WT patients. 相似文献
16.
Dufour C Beaugrand A Le Deley MC Bourdeaut F André N Leblond P Bertozzi AI Frappaz D Rialland X Fouyssac F Edan C Grill J Quidot M Varlet P 《Cancer》2012,118(15):3812-3821
BACKGROUND:
The objective of this study was to describe the clinical and pathologic features and to identify prognostic factors in patients with atypical teratoid/rhabdoid tumors (AT/RT) of the central nervous system (CNS).METHODS:
Patients aged <18 years with newly diagnosed CNS AT/RT who were treated in France between 1998 and 2008 were retrospectively identified. The study included all patients who had a diagnosis of AT/RT confirmed by pathologic review, including immunostaining for INI 1, tumor protein 53 (p53), β‐catenin, claudin‐6, and Ki‐67 and analysis for SMARCB1/hSNF5/INI1 mutation.RESULTS:
Fifty‐eight patients with confirmed AT/RT were eligible for the current analysis. The median age at diagnosis was 1.4 years (range, 14 days to 8.5 years). The site of the primary tumor was supratentorial in 26 patients, infratentorial in 28 patients and spinal in 4 patients. Loss of INI1 nuclear expression was observed in 49 of 50 evaluable tumors. Positive claudin‐6 was observed in 37 of 42 assessed tumors and, in 12 of those tumors, the staining was strong and diffuse. Positive nuclear immunoreactivity for β‐catenin was observed in 24 of 44 tumors, and P53 was overexpressed in 31 of 44 tumors. Primary adjuvant therapy included chemotherapy in 47 patients and radiotherapy in 16 patients. The median follow‐up was 58 months (range, 9‐125 months), and the median survival was 9 months. Multivariate analysis identified age <2 years (P = .01), metastasis at diagnosis (P = .03), and strong immunopositivity for claudin‐6 (P = .03) as prognostic factors for the risk of death.CONCLUSIONS:
AT/RT tumors in children carry a dismal prognosis. Age <2 years, metastasis at diagnosis, and strong claudin‐6 positivity appeared to be independent prognostic factors for outcome. Cancer 2012. © 2011 American Cancer Society. 相似文献17.
18.
Izawa N Matsumoto S Manabe J Tanizawa T Hoshi M Shigemitsu T Machinami R Kanda H Takeuchi K Miki Y Arai M Shirahama S Kawaguchi N 《International journal of clinical oncology / Japan Society of Clinical Oncology》2008,13(1):78-82
We describe a patient who had nine primary malignant tumors and a germline mutation in the p53 tumor-suppressor gene, characteristically found in the Li-Fraumeni syndrome (LFS). A 15-year-old girl with no family history
of cancer was referred to our hospital because of pain and swelling of the right knee. Osteosarcoma was diagnosed. The patient
received chemotherapy followed by surgery and had a remission. After the age of 28 years, nine primary malignant tumors developed
successively, including right breast cancer, colon cancer, malignant fibrous histiocytoma (MFH) of the abdominal wall, right
lung double cancers, bilateral breast cancers, and MFH of the left thigh. This is the second highest number of types of primary
malignant tumors to be reported in LFS. All tumors were treated by a multidisciplinary approach, including surgery. Genetic
analysis revealed a germline missense mutation in the p53 gene (c.659 A > G), resulting in Y220C, which has been reported in three families with LFS. The patient died of lung metastasis
from MFH at the age of 37 years. Despite the multiple tumors, repeated induction of remissions resulted in long survival.
Our findings suggest that a multidisciplinary approach to treatment, including surgery, is beneficial in patients with LFS. 相似文献
19.
目的:探讨对携带BRCA1/2突变的中国健康女性实施乳腺预防性切除及I期重建的可行性。方法:选择2018年1月至2019年2月3例于北京大学国际医院就诊的携带BRCA1/2突变的中国健康女性,其中2例携带BRCA1突变、1例携带BRCA2突变,均有乳腺癌家族史,年龄为34~36岁,实施预防性保留乳头-乳晕的双侧乳腺切除和Ⅰ期假体重建术。结果:3例患者术后无并发症发生,术后中位随访时间为18个月,均无乳腺癌发生,对重建乳房外形满意,且焦虑和恐惧情绪显著下降,取得良好的疗效。结论:对携带BRCA1/2突变且有乳腺癌家族史的中国健康女性,在严格筛选的基础上,可慎重开展乳腺预防性切除及Ⅰ期重建术。 相似文献
20.
Roznowski K Januszkiewicz-Lewandowska D Mosor M Pernak M Litwiniuk M Nowak J 《Breast cancer research and treatment》2008,110(2):343-348
Nijmegen Breakage Syndrome (NBS) is a rare autosomal, recessive disease caused by homozygous mutations in the NBS1 gene. The most common deletion of 5 bp (657del5) in exon 6, which affects mostly the population of Central Europe is observed. Among the typical features of this disorder is that NBS patients experience a high incidence of lymphoid malignancies as well. An increased risk of solid tumors development for 657del5 carriers was the reason to investigate the role of NBS1 gene as a susceptible one for the breast cancer. The purpose of this work is to identify mutations in all 16 exons of the NBS1 gene in the group of the patients with diagnosed breast cancer and the control group of healthy individuals. In the group of 270 women with breast cancer, seven cases of mutated NBS1 gene were revealed. In the subgroup presenting mutated NBS1 gene, the mutation I171V in 5th exon occurred in five cases. It is the first such a discovery concerning breast cancer patients because this mutation had been previously observed only in the course of lymphoid or hematological malignancies. The rate of I171V mutation in the group of breast cancer patients was significantly higher than in the controls (OR: 9.42; 95% CI: 1.09-81.05; P = 0.02). The conclusion is that heterozygous germline mutation I171V in NBS1 gene is a significant risk factor for breast cancer development. It concerns especially the women whose first degree relatives had a previously diagnosed breast cancer (OR: 6.00; 95% CI: 0.98-38.07; P = 0.04). The histopathological and clinical features of breast cancer with I171V mutation suggest accumulation of the negative prognostic factors. The treatment's results however were unexpectedly satisfactory, that is why further investigations are necessary to assess the role of I171V mutation in NBS1 gene as a prognostic and predictive factor for breast cancer. 相似文献