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DK2582847T3 - Fremgangsmåder og materialer til at vurdere tab af heterozygositet - Google Patents

Fremgangsmåder og materialer til at vurdere tab af heterozygositet Download PDF

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DK2582847T3
DK2582847T3 DK11796544.2T DK11796544T DK2582847T3 DK 2582847 T3 DK2582847 T3 DK 2582847T3 DK 11796544 T DK11796544 T DK 11796544T DK 2582847 T3 DK2582847 T3 DK 2582847T3
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cancer cells
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Victor Abkevich
Alexander Gutin
Kirsten Timms
Jerry Lanchbury
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Myriad Genetics Inc
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Claims (14)

1. Fremgangsmåde til at forudsige en cancerpatients respons til et cancerbehandlingsregime omfattende et DNA-nedbrydningsmiddel, en anthracyclin, en topoisomerase-I-inhibitor, stråling, og/eller en PARP-inhibitor, hvilken fremgangsmåde omfatter: bestemme, i cancercellen, det samlede antal af LOH-regioner i mindst et par humane kromosomer fra denne cancercelle der er længere end en første længde men kortere end længden af det hele kromosom indeholdende LOH-regionen, hvor det mindst ene par humane kromosomer ikke er et humant X/Y kønskromosompar, hvor den første længde er ca. 15 megabaser eller derover, hvor cancercellen er valgt fra gruppen bestående af brystcancerceller, æggestokcancerceller, leukæmicancerceller, øsofagealcancerceller, lungecancerceller, og prostatacancerceller; og korrelere det samlede antal der er større end et referenceantal med en forhøjet sandsynlighed for at denne cancerpatient vil respondere til dette cancerbehandlingsregime.
2. Fremgangsmåde til at forudsige en cancerpatients respons til et behandlingsregime omfattende paclitaxel eller docetaxel, omfattende: bestemme, i cancercellen, det samlede antal af LOH-regioner i mindst et par humane kromosomer fra denne cancercelle der er længere end en første længde men kortere end længden af det hele kromosom indeholdende LOH-regionen, hvor det mindst ene par humane kromosomer ikke er et humant X/Y kønskromosompar, hvor den første længde er ca. 15 megabaser eller derover, hvor cancercellen er valgt fra gruppen bestående af brystcancerceller, æggestokcancerceller, leukæmicancerceller, øsofagealcancerceller, lungecancerceller, og prostatacancerceller; og korrelere det samlede antal der er større end et referenceantal med en forhøjet sandsynlighed for at denne cancerpatient ikke vil responderes til et behandlingsregimen omfattende paclitaxel eller docetaxel.
3. Cancerbehandling omfattende ét eller flere lægemidler valgt fra gruppen bestående af DNA-nedbrydningsmidler, anthracycliner, topoisomerase I-inhibitorer, og PARP-inhibitorer til anvendelse i behandling af cancer hos en patient med en øget sandsynlighed for respons til denne behandling, hvor bestemmelsen af hvorvidt eller ikke patienten har en øget sandsynlighed for respons til denne behandling udføres ved fremgangsmåden ifølge krav 1 eller 2.
4. Anvendelse af ét eller flere lægemidler valgt fra gruppen bestående af DNA-nedbrydningsmidler, anthracycliner, topoisomerase I-inhibitorer, og PARP-inhibitorer, til fremstillingen af et medikament til behandling af en cancer hos en patient med en øget sandsynlighed for respons til dette regime, omfattende bestemmelsen af hvorvidt eller ikke patienten har en øget sandsynlighed for respons til dette regime ved fremgangsmåden ifølge krav 1 eller 2.
5. System til at bestemme LOH-status af en cancercelle fra en cancerpatient, omfattende: (a) en prøveanalysator konfigureret til at producere en flerhed af signaler omkring genomisk DNA, hvor disse signaler identificerer den homozygote eller heterozygote beskaffenhed af loci på mindst et par humankromosomer fra denne cancercelle, og hvor cancercellen er valgt fra gruppen bestående af brystcancerceller, æggestokcancerceller, leukæmicancerceller, øsofagealcancerceller, lungecancerceller, og prostatacancerceller, og (b) et computer-undersystem programmeret til at beregne, baseret på flerheden af signaler, antallet af indikator-LOH-regioner i det mindst ene par humane kromosomer, hvor indikator-LOH-regionerne er LOH-regioner der er i et par human-kromosomer forskellig fra det humane X/Y-kønskromosompar, og er kendetegnet ved LOH med en længde på ca. 15 megabaser eller derover men kortere end længden af det hele kromosom indeholdende LOH-regionerne, og hvor dette computerundersystem er programmeret til at sammenligne dette antal af indikator-LOH-regioner med et referencetal for at bestemme en sandsynlighed for at denne cancerpatient vil respondere på et cancerbehandlingsregime omfattende et DNA-nedbrydningsmiddel, en anthracyclin, en topoisomerase-I-inhibitor, stråling, eller en PARP-inhibitor.
6. Diagnostisk kit omfattende: (a) mindst 500 oligonukleotider der er i stand til at hybridisere til en flerhed af polymorfe loci fra humant genomisk DNA; og (b) computerprogramprodukt programmeret til at beregne, baseret på en flerhed af signaler der identificerer den homozygote eller heterozygote beskaffenhed af disse loci, antallet af indikator-LOH-regioner i mindst et par humane kromosomer, hvor indikator-LOH-regionen er LOH-regioner der er i et par human-kromosomer forskellig fra det humane X/Y kønskromosompar, og er kendetegnet ved LOH med en længde på ca. 15 megabaser eller derover men kortere end længden af det hele kromosom indeholdende LOH-regionens, og hvor computerprogramproduktet er programmeret til at sammenligne dette antal af indikator-LOH-regioner med et referencetal til at bestemme sandsynligheden at en cancerpatient vil respondere på et cancerbehandlingsregime omfattende et DNA-nedbrydningsmiddel, et anthracyclin, en topoisomerase-I-inhibitor, stråling, eller en PARP-inhibitor, og hvor cancercellen er valgt fra gruppen bestående af brystcancerceller, æggestokcancerceller, leukæmicancerceller, øsofageal-cancerceller, lungecancerceller, og prostatacancerceller.
7. Anvendelse af en flerhed af oligonukleotider der er i stand til at hybridisere til en flerhed af jævnt fordelte polymorfe loci fra humant genomisk DNA for at (a) bestemme det samlede antal af Indikator-LOH-regioner i mindst et kromosompar af en human cancercelle opnået fra en cancerpatient, hvor hvert oligonukleotid hybridiserer til et specifikt polymorft locus, og hvor indikator-LOH-regionen er LOH-regioner der er i et par human-kromosomer forskellig fra det humane X/Y kønskromosompar, og er kendetegnet ved LOH med en længde på ca. 15 megabaser eller derover men kortere end længden af det hele kromosom indeholdende LOH-regionens, og hvor cancercellen er valgt fra gruppen bestående af brystcancerceller, æggestokcancerceller, leukæmicancerceller, øsofageal-cancerceller, lungecancerceller, og prostatacancerceller; og (b) påvise en øget sandsynlighed for at denne cancerpatient vil respondere på et cancerbehandlingsregime omfattende et DNA-nedbrydningsmiddel, et anthracyclin, en topoisomerase-I-inhibitor, stråling, eller en PARP-inhibitor.
8. Fremgangsmåden ifølge krav 1 eller 2, systemet ifølge krav 5, kittet ifølge krav 6, eller anvendelsen ifølge krav 7, hvor LOH-regionerne eller Indikator-LOH-regionerne bestemmes i mindst to, fem, ti eller 21 par af humane kromosomer.
9. Fremgangsmåden ifølge krav 1 eller 2, systemet ifølge krav 5, kittet ifølge krav 6, eller anvendelsen ifølge krav 7, hvor det samlede antal af LOH-regioner eller Indikator-LOH-regioner er 9, 15, 20 eller derover.
10. Fremgangsmåden ifølge krav 1 eller 2, systemet ifølge krav 5 eller kittet ifølge krav 6, hvor referencetallet er 6, 7, 8, 9, 10, 11, 12 eller 13 eller derover.
11. Fremgangsmåden ifølge krav 1 eller 2, systemet ifølge krav 5, kittet ifølge krav 6, eller anvendelsen ifølge krav 7, hvor det mindst ene par humane kromosomer ikke er human kromosom 17.
12. Systemet ifølge krav 5, kittet ifølge krav 6, eller anvendelsen ifølge krav 7, hvor indikator-LOH-regionen ikke er i human kromosom 17.
13. Fremgangsmåden ifølge krav 1, cancerbehandlingsregime til anvendelse af ifølge 3, eller anvendelsen ifølge krav 4, hvor DNA-nedbrydningsmidlet er cisplatin, carboplatin, oxalaplatin, eller picoplatin, hvilken anthracyclin er epirubicin eller doxorubicin, topoisomerase-I-inhibitoren er campothecin, topotecan, eller irinotecan, eller PARP-inhibitoren er iniparib, olaparib eller veliparib.
14. Systemet ifølge krav 5, kittet ifølge krav 6, eller anvendelsen ifølge krav 7, hvor DNA-nedbrydningsmidlet er et platin-baseret kemoterapilægemiddel, hvilken anthracyclin er epirubicin eller doxorubicin, topoisomerase-I-inhibitoren er campothecin, topotecan, eller irinotecan, eller PARP-inhibitoren er iniparib, olaparib eller veliparib.
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