CN102424848A - Probe combination for diagnosing Xp11.2 translocation renal cancer and application thereof - Google Patents
Probe combination for diagnosing Xp11.2 translocation renal cancer and application thereof Download PDFInfo
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Abstract
The invention discloses a probe combination for diagnosing Xp11.2 translocation renal cancer and an application thereof, which belong to the field of fluorescent in situ hybridization probe application. The probe combination is BAC cloning fragments RP11-58H17, RP11-352D11, RP11-416B14 and RP11-107C19. The specificity and the sensibility of the Xp11.2 translocation renal cancer diagnosis by the probe combination respectively reach 100 percent, convenience, high speed and reliability are realized, in addition, the success ratio is high, and the probe combination can be used for preparing Xp11.2 translocation renal cancer diagnosis reagents.
Description
Technical field
The invention belongs to the fluorescence in situ hybridization probe Application Areas, relate to a kind of probe combinations that is used for diagnosing Xp11.2 transposition property kidney and in the application of preparation Xp11.2 transposition property kidney diagnostic reagent.
Background technology
WHO revised renal cell carcinoma histopathology classification in 1997 in 2004, had increased Xp11.2 transposition/TFE3 gene fusion dependency kidney (Xp11.2 transposition property kidney) newly, this rare tumor types.Though its overall sickness rate is very low, about 1/3 is this type of kidney in children's patients with renal cell carcinoma, and retrospective study shows that this type of tumour is unrare in China.This project application people diagnosed and had reported 11 these tumours of example at home first with the method for immunohistochemical methods in 2007.Up-to-date research shows that the prognosis of Xp11.2 transposition property kidney is than non-Xp11.2 transposition property kidney poor prognosis.And the prognosis of different genes type Xp11.2 transposition property kidney is distinguished to some extent.In addition; Patient that clear and definite evidence shows Xp11.2 transposition property kidney is arranged to vascular endothelial growth factor receptor (vascular endothelial growth factor receptor; VEGFR) or the Mammals rapamycin (mammalian target of rapamycin, mTOR) molecular targeted treatment is responsive.Other there are some researches show that the MET Tyrosylprotein kinase is the target gene of ASPL-TFE3 fusion gene, and is expected to become the treatment target spot of Xp11.2 transposition property kidney.Therefore according to genotype, coming accurately, this type of tumour of diagnosis seems very important.
The molecular pathology characteristic of this tumour is to exist to comprise Xp11.2 in interior chromosome translocation, finally all causes comprising the TFE3 transcription factor gene in interior gene fusion.Have at least 7 kinds of different transposition forms to be in the news at present, but clear and definite site have only 5 kinds, comprise t (X; 1) (p11.2; Q21), cause PRCC and TFE3 gene fusion; T (X; 17) (p11.2; Q25), cause ASPL and TFE3 gene fusion; T (X; 1) (p11.2; P34), cause PSF and TFE3 gene fusion; Inv (X) (p11; Q12), cause NonO (p54nrb) and TFE3 gene fusion; T (X; 17) (p11.2; Q23), cause the CLTC-TFE3 gene fusion.Think because the conversion of promotor the final high expression level TFE3 of these fusion genes fusion rotein at present.Therefore using immunohistochemical methods detection nucleus TFE3 fusion rotein is one of current diagnosis Xp11.2 transposition property kidney important method.But its shortcoming is this method receives multiple factor affecting easily, like fixation of tissue time, tissue repair mode, antibody cloning number and artificial interpretation factor or the like.Make the possibility of result false positive or false negative occur.Especially diagnosis is often difficult more when the histology form is not true to type.
In addition; Through discovering to fusion gene mRNA; The node of all fusions of such tumour or transposition all is positioned at the starting point or the terminal point of exon, so we can't know the fusion and the transposition node of dna level, also just can not detect fusion gene with the method for PCR at dna level.Because this tumour is rare relatively, therefore difficult flesh tissue sample that obtains adopts the RT-PCR method to detect the TFE3 fusion gene, or judges that through the observation of cell caryogram diagnostic method of fusion gene type is actually rare in the work, and its operation is not convenient yet.More accurately and easily the molecular pathology diagnostic method awaits further foundation.
Chromosome fluorescence in-situ hybridization (FISH) starts from the traditional cytogenetics and the combination of dna technique, and rapid sensitive, specificity are good, can detect concealment or small chromosome aberration and complicated caryogram; Can also use multiple fluorescent mark, show relative position and direction between dna fragmentation and the gene, spatial positioning is accurate.In addition, the method for FISH can be carried out retrospective study on paraffin-embedded sample, greatly reduces the requirement to the research sample.At present, utilize fluorescence in situ hybridization (FISH) to diagnose the external report of method of this tumour less, domesticly do not appear in the newspapers as yet.
Similar probe in the foreign literature:
[1]Argani?P，Aulmann?S，Karanjawala?Z，Fraser?RB，Ladanyi?M，Rodriguez?MM.Melanotic?Xp11?translocation?renal?cancers：a?distinctive?neoplasm?with?overlapping?features?of?PEComa，carcinoma，and?melanoma.Am?J?Surg?Pathol.2009?Apr；33(4)：609-619.
S?Aulmann，T?Longerich，P?Schirmacher，G?Mechtersheimer?&?R?Penzel?Detection?of?the?ASPSCR1-TFE3?gene?fusion?in?paraffin-embedded?alveolar?soft?part?sarcomasHistopathology?2007，50，881-886.
Used probe: RPCI11-211H10, RPCI11-58H17, RPCI11-122 N23, RPCI-57A11 (kinetochore end) RPCI11-552E4, RPCI11-344N17, RPCI11-735G22 (telomere end).
Estimate: this probe has used more cloned sequence expensive, and only in 2 routine Xp11.2 transposition/TFE3 gene fusion dependency kidneys and 5 routine alveolar soft part sarcomas, verifies.
[2]Zhong?M，De?Angelo?P，Osborne?L，Keane-Tarchichi?M，Goldfischer?M，Edelmann?L，Yang?Y，Linehan?WM，Merino?MJ，Aisner?S，Hameed?M.Dual-color，break-apart?FISH?assay?on?paraffin-embedded?tissues?as?an?adjunct?to?diagnosis?of?Xp11?translocation?renal?cell?carcinoma?and?alveolar?soft?part?sarcoma.Am?J?Surg?Pathol.2010?Jun；34(6)：757-766.
Used probe: RP11-404P16 (458kb) and RP11-416B14 (182kb) telomere end RP11-528A24 (116kb) and RP11-58H17 (182kb) kinetochore end
Estimate: the cloned sequence of this probe is not of uniform size, and maximum and the kb more than 300 that differs minimum are easy to generate the heterogeneity of in situ hybridization condition.And only in 5 routine Xp11.2 transposition/TFE3 gene fusion dependency kidneys and 2 routine alveolar soft part sarcomas, verified.
Summary of the invention
The objective of the invention is provides a kind of probe combinations that is used to diagnose Xp11.2 transposition property kidney to above-mentioned technical problem.
Another object of the present invention provides the application of above-mentioned probe combinations in preparation Xp11.2 transposition property kidney diagnostic reagent.
Further object of the present invention provides the diagnostic kit that contains above-mentioned probe combinations.
The objective of the invention is to realize through following technical proposal:
A kind of probe combinations that is used to diagnose Xp11.2 transposition property kidney, this is combined as BAC clone segment (perhaps being BAC clone probe) RP11-58H17, RP11-352D11, RP11-416B14, RP11-107C19.
Described probe combinations, wherein RP11-58H17 and RP11-352D11 are positioned TFE3 kinetochore one side, and the two is labeled as the fluorescence of any one identical color; RP11-416B14 and RP11-107C19 are positioned TFE3 telomere one side, the two be labeled as identical but with the different fluorescence of color of kinetochore one side mark.
Described probe combinations, wherein RP11-58H17 and RP11-352D11 all are labeled as green fluorescence, and RP11-416B14 and RP11-107C19 all are labeled as red fluorescence; The fluorescence color of mark can exchange.
The application of described probe in preparation Xp11.2 transposition property kidney diagnostic reagent.
A kind of Xp11.2 transposition property kidney diagnostic kit is characterized in that this test kit comprises the described probe of claim 1.
Below be the detailed explanation of technical scheme of the present invention:
The probe combinations that the present invention adopts is different with prior art, is based on the analysis of situation such as distributing position to the different BAC cloned sequence binding site at TFE3 gene two ends on the karyomit(e), size and the preferred version taked.
Among the present invention; TFE3 kinetochore one side BAC cloned sequence is RP11-58H17 (fragment length 200kb) and RP11-352D11 (fragment length 175kb); TFE3 telomere one side BAC cloned sequence is RP11-416B14 (fragment length 182kb) and RP11-107C19 (fragment length 160kb); These fragments are bacterial artificial chromosome (Bacterial artificial chromosome; BAC) clone; Its location on human chromosomal is open, is respectively RP11-58H17 (X chromosome 49444577-49644633) X chromosome, RP11-352D11 (X chromosome 49071535-49246795), RP11-416B14 (X chromosome 48465815-48648142), RP11-107C19 (X chromosome 48172092-48332445).The orientating as of TFE3 gene (X chromosome 48771185-48787934).The BAC cloned sequence is RP11-58H17, RP11-352D11, TFE3, RP11-416B14, RP11-107C19 (the side direction telomere side direction from the kinetochore) in proper order with linking of TFE3 gene.
Keep certain distance between the bonded BAC cloned sequence and between the adjacent BAC cloned sequence on TFE3 gene and the karyomit(e) and can overlapping (be 283kb among the present invention to the maximum, minimum is not 98kb).Like this, because the BAC cloned sequence size that adopts close (among the present invention minimum and maximum between differ be merely 40kb), maximum distance is controlled in the 1500kb between the BAC cloned sequence of two ends; Have proper spacing each other, make when carrying out Fluirescence observation, two BAC cloned sequences of telomere side show a kind of fluorescence; Like redness, side two BAC cloned sequences in kinetochore show another kind of fluorescence, like green; When non-Xp11.2 transposition property kidney, the TFE3 gene does not rupture, and red green two kinds of fluorescence lean on closerly; Red green fusion signal (showing as red green linking to each other or the yellow signal point) appears during observation, and when Xp11.2 transposition property kidney, the TFE3 gene break; Cause red green two kinds of fluorescence to leave distantly, need not during observation to amplify and to see separation red green two kinds of signals far away, be easy to observe.
The BAC cloned sequence that connects the fluorescence of 2 mark colors of the same race at the every end of X chromosome TFE3 gene is in order to strengthen fluorescence intensity and scope; Through experimental observation; The fluorescence intensity of 2 BAC cloned sequences and scope are enough observed; Both avoid 1 BAC cloned sequence the too small situation of the not enough scope of fluorescence intensity possibly occur, and avoided adopting a plurality of BAC cloned sequences can cause the fluorescence scope to disperse to be easy to generate to disturb and the also higher drawback of cost again.
Select these 4 kinds of BAC cloned sequences that the consideration of the following aspects is arranged: 1. these several BAC cloned sequence sizes are close, and the benefit of bringing is: the fluorescence intensity of each end is consistent, and prevent that the end from crossing strong and the other end is crossed weak and influence is observed; The in situ hybridization condition is kept consistency.2. binding site makes between the adjacent BAC cloned sequence and can keep suitable distance, can strengthen each end fluorescence intensity and scope.TFE3 gene two ends BAC cloned sequence maximum distance is controlled within the 1500kb; There is the TFE3 gene between two kinds of fluorescence colors; Make when the TFE3 gene does not rupture, to appear and merge signal (as showing as red green linking to each other or the yellow signal point); And two kinds of fluorescence color separation are distant when the TFE3 gene break, are easy to observe.Otherwise if TFE3 gene two ends BAC cloned sequence maximum distance is excessive, as surpassing 1500kb even bigger, then no matter whether the TFE3 gene ruptures, and all observes obviously isolating two kinds of fluorescence, just is difficult to judge whether to exist Xp11.2 transposition property kidney.
BAC cloned sequence mark fluorescent is convenient to adopt fluorescence microscope, and is convenient directly perceived.Certainly, the BAC cloned sequence also is not limited to mark fluorescent, can be marked as the used affinity tag of corresponding detection technique when adopting other detection techniques.
Beneficial effect of the present invention:
The present invention is according to the characteristics of Xp11.2 transposition property kidney; Design is combined in the fluorescent label DNA probe combinations at TFE3 gene two ends; On the basis of paraffin-embedded tissue section, carry out in situ hybridization, detect and merge and separation signal, can improve the accuracy rate of such tumour of diagnosis greatly.For molecular targeted treatment provides foundation.According to our experimental result, specificity and the susceptibility of the diagnosis of this probe combinations have all reached 100%, and operand only need carry out on paraffin-embedded tissue is cut into slices, and the time is merely two working dayss.Adopt probe combinations provided by the invention to detect Xp11.2 transposition property kidney; Not only easily and fast, reliable but also success ratio is high; Can be used for preparing Xp11.2 transposition property kidney diagnostic kit, for the diagnosis fast and accurately of Xp11.2 transposition property kidney provides new instrument.
Description of drawings
Fig. 1: BAC clone probe station-keeping mode figure.
Fig. 2: the detection figure of 3 routine Xp11.2 transposition property kidney fusion genes.
Wherein: figure A, figure B RT-PCR result show that 3 routine tumor tissues and cancer beside organism all detect an about 190-bp ASPL-TFE3 fusion gene band of size (figure A) and the about 200-bpTEF3-ASPL fusion gene band of another size (figure B); There are the balance transposition in figure C No. 17 karyomit(e)s of sequencing result demonstration and X chromosome, and ASPL-TFE3 fusion gene size is 195-bp (the ASPL exon 7 links to each other with TFE3 exon 4).TEF3-ASPL fusion gene size is 218-bp (the TFE3 exon 3 links to each other with ASPL exon 8).
Fig. 3: the plat of organization chip.
Fig. 4: visible 2 red green fusion signals in normal each nucleus of women's nephridial tissue (the red green lap of arrow indication shows as yellow, amplify the back observe real for lean on very near red and green signals), represent 2 X chromosomes all complete.
Fig. 5: visible 1 red green fusion signal in each nucleus of normal male nephridial tissue (the red green lap of arrow indication shows as yellow, amplify the back observe real for lean on very near red and green signals), represent 1 X chromosome complete.
Fig. 6: visible 1 red green fusion signal in each nucleus in male sex's Papillary Renal Cell Carcinoma (the red green lap of arrow indication shows as yellow, amplify the back observe real for lean on very near red and green signals), the green separation signal of show not.
Fig. 7: visible 1 red green fusion signal in each nucleus in male sex's clear cell carcinoma of kidney (the red green lap of arrow indication shows as yellow, amplify the back observe real for lean on very near red and green signals), the green separation signal of show not.
Fig. 8: visible 1 pair of red green separation signal in (male sex) Xp11.2 transposition property kidney tumor tissue cell nuclear (need not to amplify can clearly observe red and green signals separate far away), represent an X chromosome TFE3 gene break.
Fig. 9: (red green lap shows as yellow to visible 1 the red green fusion signal of arrow indication in (women) Xp11.2 transposition property kidney tumor tissue cell nuclear; Amplify the back observe real for lean on very near red and green signals) with 1 pair of red green separation signal (need not amplification can clearly observe red and green signals separate far away), represent complete and another X chromosome TFE3 gene break of X chromosome.
Embodiment
Below through embodiment the present invention is done further elaboration.
Probe described in the embodiment is the BAC cloned sequence, also can be the BAC clone probe.
The preparation of embodiment 1:DNA probe combinations:
2 BAC cloned sequences that selection can connect respectively at X chromosome TFE3 gene two ends, maximum distance keeps certain distance not overlapping in 1500kb between the probe of control two ends between the BAC cloned sequence, and clip size is close.The cloned sequence source is the human BAC clone center (http://www.empiregenomics.com/helixhq/clonecentral/search/human) of EmpireGenomics company.TFE3 kinetochore one side BAC clone segment is RP11-58H17 (200kb) and RP11-352D11 (175kb), and TFE3 telomere one side BAC clone segment is RP11-416B14 (182kb) and RP11-107C19 (160kb).The BAC cloned sequence is RP11-58H17, RP11-352D11, TFE3, RP11-416B14, RP11-107C19 in proper order with linking of TFE3 gene.The locating structure of probe combinations is as shown in Figure 1.Utilize the nick translation method two BAC cloned sequences of telomere side to be marked as the fluorescence of any one identical color; Preferred red fluorescence; With two BAC cloned sequences of kinetochore side be marked as identical but with the different fluorescence of color of kinetochore one side mark, preferred green fluorescence; The fluorescence color of two ends mark can exchange.This method is well known to those skilled in the art (the BAC cloned sequence of mark fluorescent is provided by U.S. EmpireGenomics company).TFE3 kinetochore two BAC cloned sequences of one side are a green fluorescence signal under fluorescent microscope, represent TFE3 gene kinetochore side.Two BAC cloned sequences of TFE3 telomere one side are a red fluorescence signal under fluorescent microscope, represent TFE3 gene telomere side.The fluorescence color of two ends mark can exchange.Red and green signals is continuous or overlapping for merging signal under the normal circumstances, when Xp11.2 transposition property kidney, because the transposition of X chromosome TFE3 gene break makes red and green signals separate.
Further, can the probe combinations of preparation be adopted fluorescence in-situ hybridization method, whether its location of checking and/or diagnosis effect be reliable in Xp11.2 transposition property kidney, non-Xp11.2 transposition property kidney and cancer beside organism.
Embodiment 2: the fluorescence in situ hybridization process:
One, the organization chip of sample makes up:
Collect Nanjing General Hospital, Nanjing Military Area Command, PLA's diagnosing renal cell carcinoma 51 examples.Positive by two veteran pathologist with reference to WHO 2004 uropoiesis and male reproductive system criteria for classification, immunohistochemical methods TFE3, and RT-PCR detect fusion gene result (Fig. 2 A, B, C; It is to have obtained diagnosis in the mRNA aspect that 3 examples are arranged among the 51 routine patients; With the mutual corresponding safety that more can embody this experiment of this experimental result); Again carry out diagnostic assessment; Last diagnostic Xp11.2 transposition property kidney 24 examples, clear cell carcinoma 9 examples, palilate kidney 17 examples (wherein sporadic palilate kidney 16 examples, the sick dependency palilate of VHL kidney 1 example), unclassified renal cell carcinoma 1 example as a result.Above sample (comprising cancer and cancer beside organism) is made into organization chip (Fig. 3).
Two, fluorescence in situ hybridization:
The thick section of organization chip 3 μ m after dewaxing, places 100%, 85%, 70% each 2min of ethanol successively, immerses in the deionized water 100 ℃ of water-bath 15min subsequently.Tissue slice is put into 37 ℃ of stomach en-K solution (0.1g stomach en-, 40ml 0.01M HCL), 15min; 2 * SSC (sodium-chlor, Trisodium Citrate) rinsing 2 times, each 5min, section places 0.1mol/L HCl soaking at room temperature 10min, with 2 * SSC rinsing 2 times, each 5min; Through 70%, 85%, the 100% ethanol 2min that respectively dewaters, in air drying; Mixed solution (each the 0.5 μ l of each probe wherein that adds the above-mentioned fluorescently-labeled probe of 10ul at tissue regions; 4 probes are totally 2 μ l; Other adds the hybridization buffer of 8 μ l, and hybridization buffer is provided by EmpireGenomics company when buying fluorescence labeling probe, includes human Cot1 DNA); Add deckglass, use the rubber adhesive edge; Put into 37 ℃ spend the night (16h) behind 88 ℃ of sex change 6min of in situ hybridization appearance (GeneAmp In Situ PCR System 1000); Remove deckglass, slide is placed 0.4 * SSC (sodium-chlor, Trisodium Citrate, 0.3%NP-40) solution, 69 ℃ of rinsing 1min; Rinsing 1min in 2 * SSC (sodium-chlor, Trisodium Citrate, 0.1%NP-40) solution, 70% ethanol 3min, the room temperature dark place is dry; Target region drips 10 μ l 4 ', 6-diamidino-2-phenylindone (4 ', 6-diamidino-2-phenylindole DAPI), after the deckglass mounting, use the fluorescence microscope result again.
The result judges:
The normal cell X chromosome, visible 1 the red green fusion signal of male sex's sample, visible 2 the red green fusion signals of women show as red green linking to each other or the yellow signal point.
Tumour cell, the visible a pair of red green isolating abnormal signal of male sex's sample, a visible normal signal and a pair of unusual red green separation signal of merging of women.
For getting rid of false positive and false negative; 100 cells of each sample counting have only when 4 fluorescent signals (women) or 2 fluorescent signals (male sex) when all existing, and just include the counting object in (in the women; We all can see 4 single signals (two green and two red) normal and tumour; Be to merge in pairs only, look that being two merges signals, but actually form by four single signals at normal women's red and green signals.In tumour, seeing one and merge signal and a pair of red green isolating single signal, is 3 signals outwardly, but reality still is what be made up of 4 single signals).Distance between the red green fluorescence signal is counted separation signal during greater than a deration of signal.When abnormal signal is designated as the positive greater than 10% the time.The judgment criteria that the most on the market similarly commercialization probes of the above foundation of determination methods are as a result exercised is like the probe method of use of Vysis company and Dako company.
The result:
We detect 51 routine kidneys, wherein Xp11.2 transposition property kidney 24 examples, clear cell carcinoma 9 examples, palilate kidney 17 examples (wherein sporadic palilate kidney 16 examples, the sick dependency palilate of VHL kidney 1 example), unclassified renal cell carcinoma 1 example.24 routine Xp11.2 transposition property kidneys all detect unusual separation signal as a result; (visual field that fluorescent microscope can't provide 100 cells supplies the people to observe to its positive cell number scope at 20%-85%; Therefore the data of 20%-85% can only be examined repeatedly to count and get), the other normal kidney tissue of all the other tumours and cancer does not all detect abnormal signal (Fig. 2-9 has provided the representative positive picture of organization chip, the male sex and women Xp11.2 transposition property kidney, all the other tumours such as the negative picture of clear cell carcinoma and palilate kidney, the negative picture of men and women's normal kidney tissue).Explain and use the specificity and the susceptibility of this probe in detecting Xp11.2 transposition property kidney to be all 100%
Susceptibility=true positives/all Xp11.2 transposition property kidney oncosis number * 100%; 24 true positives case/24Xp11.2 transposition property kidney=100%;
Specificity=true negative/all non-Xp11.2 transposition property kidney oncosis number * 100%; 27 true negative case/27 non-Xp11.2 transposition property kidney tumour patient.
Estimate:
The cloned sequence that this group probe uses is less relatively, and the cloned sequence size is consistent relatively, differs between minimum and maximum and is merely 40kb.In design, considered that promptly economy considered the consistence of in situ hybridization condition again.In addition, the specificity of the double-colored break apart fluorescence in situ hybridization probe of TFE3 and susceptibility have all reached 100% in this experiment.Utilize the FISH technology, use the double-colored break apart fluorescence in situ hybridization probe of TFE3 to diagnose Xp11.2 transposition property kidney.Fast, reliable and success ratio is high, be a new technology of diagnosis Xp11.2 transposition property kidney, be worthy to be popularized.
Embodiment 3:Xp11.2 transposition property kidney diagnostic kit
Contain embodiment 1 described probe combinations in the test kit, the characteristic of this probe combinations mainly is:
(1) TFE3 kinetochore one side BAC clone probe is RP11-58H17 (fragment length 200kb) and RP11-352D11 (fragment length 175kb), the mark green fluorescence.These two probes are a green fluorescence signal under fluorescent microscope, represent TFE3 gene kinetochore side.
(2) TFE3 telomere one side BAC clone probe is RP11-416B14 (fragment length 182kb) and RP11-107C19 (fragment length 160kb), the mark red fluorescence.These two probes are a red fluorescence signal under fluorescent microscope, represent TFE3 gene telomere side.
(3) red and green signals is continuous or overlapping for merging signal under the normal circumstances, when Xp11.2 transposition property kidney, because the transposition of X chromosome TFE3 gene break makes red and green signals separate.
Claims (5)
1. a probe combinations that is used to diagnose Xp11.2 transposition property kidney is characterized in that this probe combinations is BAC clone segment RP11-58H17, RP11-352D11, RP11-416B14, RP11-107C19.
2. probe combinations according to claim 1 is characterized in that RP11-58H17 and RP11-352D11 are positioned TFE3 kinetochore one side, and the two is labeled as the fluorescence of any one identical color; RP11-416B14 and RP11-107C19 are positioned TFE3 telomere one side, the two be labeled as identical but with the different fluorescence of color of kinetochore one side mark.
3. probe combinations according to claim 2 is characterized in that RP11-58H17 and RP11-352D11 all are labeled as green fluorescence, and RP11-416B14 and RP11-107C19 all are labeled as red fluorescence; The fluorescence color of mark can exchange.
4. the application of the described probe of claim 1 in preparation Xp11.2 transposition property kidney diagnostic reagent.
5. an Xp11.2 transposition property kidney diagnostic kit is characterized in that this test kit comprises the described probe of claim 1.
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