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1. 发明申请

US20120077694A1 TARGETS IN BREAST CANCER FOR PROGNOSIS OR THERAPY 审中-公开
标题翻译：乳腺癌中的目标用于预防或治疗
公开(公告)号：US20120077694A1
公开(公告)日：2012-03-29
申请号：US13243712
申请日：2011-09-23
申请人： Joe W. Gray , Jane Fridlyand , Richard Neve , Paul Spellman , Koei Chin , Zhi Hu , Frederic Waldman
发明人： Joe W. Gray , Jane Fridlyand , Richard Neve , Paul Spellman , Koei Chin , Zhi Hu , Frederic Waldman
IPC分类号： C40B30/04 , G01N33/566 , C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/112 , C12Q2600/118 , C12Q2600/136
摘要： Cancer markers are developed to detect diseases characterized by increased expression of apoptosis-suppressing genes, such as aggressive cancers. Genome wide analyses of genome copy number and gene expression in breast cancer revealed 66 genes in the human chromosomal regions, 8p11, 11q13, 17q12, and 20q13 that were amplified. Diagnosis and assessment of amplification levels of genes shown to be amplified are useful in prediction of patient outcome of a of patient's response and drug resistance in breast cancer. Certain genes were found to be high priority therapeutic targets by the identification of recurrent aberrations involving genome sequence, copy number and/or gene expression are associated with reduced survival duration in certain diseases and cancers, specifically breast cancer. Inhibitors of these genes will be useful therapies for treatment of these non-responsive cancers.
摘要翻译：癌症标志物被开发用于检测特征在于凋亡抑制基因如侵袭性癌症的表达增加的疾病。在乳腺癌基因组拷贝数和基因表达的基因组分析中，发现人染色体区域中的66个基因，8p11,11q13,17q12和20q13被扩增。显示扩增的基因的扩增水平的诊断和评估可用于预测患者在乳腺癌中的反应和耐药性的结果。通过鉴定涉及基因组序列的复发性畸变，拷贝数和/或基因表达与某些疾病和癌症特别是乳腺癌中的存活时间减少有关，某些基因被认为是高度优先的治疗靶点。这些基因的抑制剂将是治疗这些非反应性癌症的有用治疗方法。

2. 发明申请

US20060257895A1 Detection of chromosomal abnormalities associated with breast cancer 失效
标题翻译：检测与乳腺癌相关的染色体异常
公开(公告)号：US20060257895A1
公开(公告)日：2006-11-16
申请号：US11361316
申请日：2006-02-24
申请人： Daniel Pinkel , Joe Gray , Anne Kallioniemi , Ollie-Pekka Kallioniemi , Frederic Waldman , Masaru Sakamoto
发明人： Daniel Pinkel , Joe Gray , Anne Kallioniemi , Ollie-Pekka Kallioniemi , Frederic Waldman , Masaru Sakamoto
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6809 , C12Q1/6841 , C12Q1/6886 , C12Q2600/156 , G06F15/025 , Y10S436/813 , C12Q2545/114 , C12Q2537/157
摘要： Disclosed are new methods comprising the use of in situ hybridization to detect abnormal nucleic acid sequence copy numbers in one or more genomes wherein repetitive sequences that bind to multiple loci in a reference chromosome spread are either substantially removed and/or their hybridization signals suppressed. The invention termed Comparative Genomic Hybridization (CGH) provides for methods of determining the relative number of copies of nucleic acid sequences in one or more subject genomes or portions thereof (for example, a tumor cell) as a function of the location of those sequences in a reference genome (for example, a normal human genome). The intensity(ies) of the signals from each labeled subject nucleic acid and/or the differences in the ratios between different signals from the labeled subject nucleic acid sequences are compared to determine the relative copy numbers of the nucleic acid sequences in the one or more subject genomes as a function of position along the reference chromosome spread. Amplifications, duplications and/or deletions in the subject genome(s) can be detected. Also provided is a method of determining the absolute copy numbers of substantially all RNA or DNA sequences in subject cell(s) or cell population(s).
摘要翻译：公开了包括使用原位杂交来检测一个或多个基因组中的异常核酸序列拷贝数的新方法，其中结合参考染色体扩增的多个基因座的重复序列基本上被去除和/或其杂交信号被抑制。称为比较基因组杂交（CGH）的发明提供了确定一个或多个受试者基因组或其部分（例如肿瘤细胞）中核酸序列的相对拷贝数的方法，作为这些序列的位置的函数参考基因组（例如，正常人类基因组）。比较来自每个标记的对象核酸的信号的强度和/或来自标记的目标核酸序列的不同信号之间的比率差异，以确定一个或多个核酸序列中核酸序列的相对拷贝数主题基因组作为沿着参考染色体扩散的位置的函数。可以检测主题基因组中的扩增，重复和/或缺失。还提供了确定受试细胞或细胞群体中基本上所有RNA或DNA序列的绝对拷贝数的方法。

3. 发明申请

US20060063168A1 Detection of nucleic acid sequence differences by comparative genomic hybridization 有权
公开(公告)号：US20060063168A1
公开(公告)日：2006-03-23
申请号：US11060644
申请日：2005-02-16
申请人： Donna Albertson , Daniel Pinkel , Jane Fridyland , Bing Huey , Antoine Snijders , Joe Gray , Anne Kallioniemi , Olli-Pekka Kallioniemi , Frederic Waldman
发明人： Donna Albertson , Daniel Pinkel , Jane Fridyland , Bing Huey , Antoine Snijders , Joe Gray , Anne Kallioniemi , Olli-Pekka Kallioniemi , Frederic Waldman
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6841 , C12Q2600/156 , C12Q2565/601
摘要： The present invention provides a method of detecting nucleotide sequence differences between two nucleic acid samples. The method employs a comparative genomic hybridization (CGH) technique to analyze the sequence differences between the samples. This method permits the identification of small sequence differences (e.g., sequence divergence of 1% or less) in nucleic acid samples of high complexity (e.g., an entire genome).

4. 发明授权

US5965362A Comparative genomic hybridization (CGH) 失效
公开(公告)号：US5965362A
公开(公告)日：1999-10-12
申请号：US562965
申请日：1995-11-27
申请人： Daniel Pinkel , Joe W. Gray , Anne Kallioniemi , Olli-Pekka Kallioniemi , Frederic Waldman , Masaru Sakamoto
发明人： Daniel Pinkel , Joe W. Gray , Anne Kallioniemi , Olli-Pekka Kallioniemi , Frederic Waldman , Masaru Sakamoto
IPC分类号： C12Q1/68 , G06F15/02 , A61K49/00 , C07H21/02 , C12P19/34
CPC分类号： C12Q1/6809 , C12Q1/6841 , C12Q1/6886 , G06F15/025 , C12Q2600/156 , Y10S436/813
摘要： Disclosed are new methods comprising the use of in situ hybridization to detect abnormal nucleic acid sequence copy numbers in one or more genomes wherein repetitive sequences that bind to multiple loci in a reference chromosome spread are either substantially removed and/or their hybridization signals suppressed. The invention termed Comparative Genomic Hybridization (CGH) provides for methods of determining the relative number of copies of nucleic acid sequences in one or more subject genomes or portions thereof (for example, a tumor cell) as a function of the location of those sequences in a reference genome (for example, a normal human genome). The intensity(ies) of the signals from each labeled subject nucleic acid and/or the differences in the ratios between different signals from the labeled subject nucleic acid sequences are compared to determine the relative copy numbers of the nucleic acid sequences in the one or more subject genomes as a function of position along the reference chromosome spread. Amplifications, duplications and/or deletions in the subject genome(s) can be detected. Also provided is a method of determining the absolute copy numbers of substantially all RNA or DNA sequences in subject cell(s) or cell population(s).

5. 发明申请

US20110130296A1 MULTI-GENE CLASSIFIERS AND PROGNOSTIC INDICATORS FOR CANCERS 审中-公开
标题翻译：多基因分类和癌症预后指标
公开(公告)号：US20110130296A1
公开(公告)日：2011-06-02
申请号：US12922651
申请日：2009-03-10
申请人： Christopher Benz , Laura Esserman , Frederic Waldman , Christina Yau
发明人： Christopher Benz , Laura Esserman , Frederic Waldman , Christina Yau
IPC分类号： C40B30/00 , C40B40/06 , C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/118 , C12Q2600/136 , C12Q2600/158
摘要： The present invention relates to the identification of marker genes useful in the diagnosis and prognosis of clinically problematic subsets of primary breast cancers. More specifically, the invention relates to the identification of two sets of marker genes that are differentially expressed in and useful for the diagnosis and prognosis of subsets of hormone receptor-negative (HRneg; i.e., ER and PR negative) and triple-negative (Tneg; i.e., ER, PR and HER2 negative) primary breast cancers at highest risk for early metastatic relapse. The invention further provides methods for determining the best course of treatment for patients having one of these clinically problematic subsets of primary breast cancers. The invention also provides methods for identifying compounds that prevent or treat a subtype of breast cancer based on their ability to modulate the activity or expression level of one or more marker genes identified herein.
摘要翻译：本发明涉及可用于诊断和预后的原发性乳腺癌临床问题亚群的标记基因的鉴定。更具体地，本发明涉及两组标记基因的鉴定，所述两组标记基因差异表达并且可用于激素受体阴性（HRneg;即ER和PR阴性）和三阴性（Tneg）的子集的诊断和预后 ;即ER，PR和HER2阴性）原发性乳腺癌患有早期转移性复发的最高风险。本发明还提供了确定患有这些临床上有问题的原发性乳腺癌亚型之一的患者的最佳治疗方案的方法。本发明还提供了基于其调节本文鉴定的一种或多种标记基因的活性或表达水平的能力来鉴定预防或治疗乳腺癌亚型的化合物的方法。

6. 发明申请

US20050118634A1 Comparative genomic hybridization 失效
标题翻译：比较基因组杂交
公开(公告)号：US20050118634A1
公开(公告)日：2005-06-02
申请号：US11017493
申请日：2004-12-17
申请人： Daniel Pinkel , Joe Gray , Anne Kallioniemi , Olli-Pekka Kallioniemi , Frederic Waldman
发明人： Daniel Pinkel , Joe Gray , Anne Kallioniemi , Olli-Pekka Kallioniemi , Frederic Waldman
IPC分类号： C12N15/09 , C07H21/04 , C12Q1/68 , C12P19/34 , G01N33/48 , G01N33/50 , G06F19/00
CPC分类号： C12Q1/6841 , C12Q1/6809 , C12Q1/6853 , C12Q1/6886 , C12Q2600/158 , C12Q2545/114 , C12Q2545/113 , C12Q2537/143 , C12Q2525/151 , C12Q2563/107
摘要： Disclosed are new methods comprising the use of in situ hybridization to detect abnormal nucleic acid sequence copy numbers in one or more genomes wherein repetitive sequences that bind to multiple loci in a reference chromosome spread are either substantially removed and/or their hybridization signals suppressed. The invention termed Comparative Genomic Hybridization (CGH) provides for methods of determining the relative number of copies of nucleic acid sequences in one or more subject genomes or portions thereof (for example, a tumor cell) as a function of the location of those sequences in a reference genome (for example, a normal human genome). The intensity(ies) of the signals from each labeled subject nucleic acid and/or the differences in the ratios between different signals from the labeled subject nucleic acid sequences are compared to determine the relative copy numbers of the nucleic acid sequences in the one or more subject genomes as a function of position along the reference chromosome spread. Amplifications, duplications and/or deletions in the subject genome(s) can be detected. Also provided is a method of determining the absolute copy numbers of substantially all RNA or DNA sequences in subject cell(s) or cell population(s).
摘要翻译：公开了包括使用原位杂交来检测一个或多个基因组中的异常核酸序列拷贝数的新方法，其中结合参考染色体扩增的多个基因座的重复序列基本上被去除和/或其杂交信号被抑制。称为比较基因组杂交（CGH）的发明提供了确定一个或多个受试者基因组或其部分（例如肿瘤细胞）中核酸序列的相对拷贝数的方法，作为这些序列的位置的函数参考基因组（例如，正常人类基因组）。比较来自每个标记的对象核酸的信号的强度和/或来自标记的目标核酸序列的不同信号之间的比率差异，以确定一个或多个核酸序列中核酸序列的相对拷贝数主题基因组作为沿着参考染色体扩散的位置的函数。可以检测主题基因组中的扩增，重复和/或缺失。还提供了确定受试细胞或细胞群体中基本上所有RNA或DNA序列的绝对拷贝数的方法。

7. 发明授权

US06335167B1 Comparative genomic hybridization (CGH) 失效
标题翻译：比较基因组杂交（CGH）
公开(公告)号：US06335167B1
公开(公告)日：2002-01-01
申请号：US09311835
申请日：1999-05-14
申请人： Daniel Pinkel , Joe W. Gray , Anne Kallioniemi , Ollie-Pekka Kallioniemi , Frederic Waldman , Masaru Sakamoto
发明人： Daniel Pinkel , Joe W. Gray , Anne Kallioniemi , Ollie-Pekka Kallioniemi , Frederic Waldman , Masaru Sakamoto
IPC分类号： C12Q168
CPC分类号： C12Q1/6809 , C12Q1/6841 , C12Q1/6886 , C12Q2600/156 , G06F15/025 , Y10S436/813 , C12Q2545/114 , C12Q2537/157
摘要： Disclosed are new methods comprising the use of in situ hybridization to detect abnormal nucleic acid sequence copy numbers in one or more genomes wherein repetitive sequences that bind to multiple loci in a reference chromosome spread are either substantially removed and/or their hybridization signals suppressed. The invention termed Comparative Genomic Hybridization (CGH) provides for methods of determining the relative number of copies of nucleic acid sequences in one or more subject genomes or portions thereof (for example, a tumor cell) as a function of the location of those sequences in a reference genome (for example, a normal human genome). The intensity(ies) of the signals from each labeled subject nucleic acid and/or the differences in the ratios between different signals from the labeled subject nucleic acid sequences are compared to determine the relative copy numbers of the nucleic acid sequences in the one or more subject genomes as a function of position along the reference chromosome spread. Amplifications, duplications and/or deletions in the subject genome(s) can be detected. Also provided is a method of determining the absolute copy numbers of substantially all RNA or DNA sequences in subject cell(s) or cell population(s).
摘要翻译：公开了包括使用原位杂交来检测一个或多个基因组中的异常核酸序列拷贝数的新方法，其中结合参考染色体扩增的多个基因座的重复序列基本上被去除和/或其杂交信号被抑制。称为比较基因组杂交（CGH）的发明提供了确定一个或多个受试者基因组或其部分（例如肿瘤细胞）中核酸序列的相对拷贝数的方法，作为这些序列的位置的函数参考基因组（例如，正常人类基因组）。比较来自每个标记的对象核酸的信号的强度和/或来自标记的目标核酸序列的不同信号之间的比率差异，以确定一个或多个核酸序列中核酸序列的相对拷贝数主题基因组作为沿着参考染色体扩散的位置的函数。可以检测主题基因组中的扩增，重复和/或缺失。还提供了确定受试细胞或细胞群体中基本上所有RNA或DNA序列的绝对拷贝数的方法。

8. 发明授权

US08021837B2 Detection of chromosomal abnormalities associated with breast cancer 失效
标题翻译：检测与乳腺癌相关的染色体异常
公开(公告)号：US08021837B2
公开(公告)日：2011-09-20
申请号：US11361316
申请日：2006-02-24
申请人： Daniel Pinkel , Joe W Gray , Anne Kallioniemi , Ollie-Pekka Kallioniemi , Frederic Waldman , Masaru Sakamoto
发明人： Daniel Pinkel , Joe W Gray , Anne Kallioniemi , Ollie-Pekka Kallioniemi , Frederic Waldman , Masaru Sakamoto
IPC分类号： C12Q1/68 , G01N33/566 , G01N33/53 , C07H21/02 , C07H21/04
CPC分类号： C12Q1/6809 , C12Q1/6841 , C12Q1/6886 , C12Q2600/156 , G06F15/025 , Y10S436/813 , C12Q2545/114 , C12Q2537/157
摘要： Disclosed are new methods comprising the use of in situ hybridization to detect abnormal nucleic acid sequence copy numbers in one or more genomes wherein repetitive sequences that bind to multiple loci in a reference chromosome spread are either substantially removed and/or their hybridization signals suppressed. The invention termed Comparative Genomic Hybridization (CGH) provides for methods of determining the relative number of copies of nucleic acid sequences in one or more subject genomes or portions thereof (for example, a tumor cell) as a function of the location of those sequences in a reference genome (for example, a normal human genome). The intensity(ies) of the signals from each labeled subject nucleic acid and/or the differences in the ratios between different signals from the labeled subject nucleic acid sequences are compared to determine the relative copy numbers of the nucleic acid sequences in the one or more subject genomes as a function of position along the reference chromosome spread. Amplifications, duplications and/or deletions in the subject genome(s) can be detected. Also provided is a method of determining the absolute copy numbers of substantially all RNA or DNA sequences in subject cell(s) or cell population(s).
摘要翻译：公开了包括使用原位杂交来检测一个或多个基因组中的异常核酸序列拷贝数的新方法，其中结合参考染色体扩增的多个基因座的重复序列基本上被去除和/或其杂交信号被抑制。称为比较基因组杂交（CGH）的发明提供了确定一个或多个受试者基因组或其部分（例如肿瘤细胞）中核酸序列的相对拷贝数的方法，作为这些序列的位置的函数参考基因组（例如，正常人类基因组）。比较来自每个标记的对象核酸的信号的强度和/或来自标记的目标核酸序列的不同信号之间的比率差异，以确定一个或多个核酸序列中核酸序列的相对拷贝数主题基因组作为沿着参考染色体扩散的位置的函数。可以检测主题基因组中的扩增，重复和/或缺失。还提供了确定受试细胞或细胞群体中基本上所有RNA或DNA序列的绝对拷贝数的方法。

9. 发明授权

US5856097A Comparative genomic hybridization (CGH) 失效
标题翻译：比较基因组杂交（CGH）
公开(公告)号：US5856097A
公开(公告)日：1999-01-05
申请号：US562898
申请日：1995-11-27
申请人： Daniel Pinkel , Joe W. Gray , Anne Kallioniemi , Olli-Pekka Kallioniemi , Frederic Waldman , Masaru Sakamoto
发明人： Daniel Pinkel , Joe W. Gray , Anne Kallioniemi , Olli-Pekka Kallioniemi , Frederic Waldman , Masaru Sakamoto
IPC分类号： C12Q1/68 , G06F15/02 , C07H21/04 , C12P19/34 , C12Q1/70
CPC分类号： C12Q1/6809 , C12Q1/6841 , C12Q1/6886 , G06F15/025 , C12Q2600/156 , Y10S436/813
摘要： Disclosed are new methods comprising the use, of in situ hybridization to detect abnormal nucleic acid sequence copy numbers in one or more genomes wherein repetitive sequences that bind to multiple loci in a reference chromosome spread are either substantially removed and/or their hybridization signals suppressed. The invention termed Comparative Genomic Hybridization (CGH) provides for methods of determining the relative number of copies of nucleic acid sequences in one or more subject genomes or portions thereof (for example, a tumor cell) as a function of the location of those sequences in a reference genome (for example, a normal human genome). The intensity(ies) of the signals from each labeled subject nucleic acid and/or the differences in the ratios between different signals from the labeled subject nucleic acid sequences are compared to determine the relative copy numbers of the nucleic acid sequences in the one or more subject genomes as a function of position along the reference chromosome spread. Amplifications, duplications and/or deletions in the subject genome(s) can be detected. Also provided is a method of determining the absolute copy numbers of substantially all RNA or DNA sequences in subject cell(s) or cell population(s).
摘要翻译：公开了包括使用原位杂交以检测一个或多个基因组中的异常核酸序列拷贝数的新方法，其中与参考染色体扩增中的多个基因座结合的重复序列基本上被去除和/或其杂交信号被抑制。称为比较基因组杂交（CGH）的发明提供了确定一个或多个受试者基因组或其部分（例如肿瘤细胞）中核酸序列的相对拷贝数的方法，作为这些序列的位置的函数参考基因组（例如，正常人类基因组）。比较来自每个标记的对象核酸的信号的强度和/或来自标记的目标核酸序列的不同信号之间的比率差异，以确定一个或多个核酸序列中核酸序列的相对拷贝数主题基因组作为沿着参考染色体扩散的位置的函数。可以检测主题基因组中的扩增，重复和/或缺失。还提供了确定受试细胞或细胞群体中基本上所有RNA或DNA序列的绝对拷贝数的方法。

10. 发明授权

US5665549A Comparative genomic hybridization (CGH) 失效
标题翻译：比较基因组杂交（CGH）
公开(公告)号：US5665549A
公开(公告)日：1997-09-09
申请号：US466122
申请日：1995-06-06
申请人： Daniel Pinkel , Joe W. Gray , Anne Kallioniemi , Olli-Pekka Kallioniemi , Frederic Waldman
发明人： Daniel Pinkel , Joe W. Gray , Anne Kallioniemi , Olli-Pekka Kallioniemi , Frederic Waldman
IPC分类号： C12N15/09 , C07H21/04 , C12Q1/68 , C07H21/02 , C12P19/34
CPC分类号： C12Q1/6841 , C12Q1/6809 , C12Q1/6853 , C12Q1/6886 , C12Q2600/158
摘要： Disclosed are new methods comprising the use of in situ hybridization to detect abnormal nucleic acid sequence copy numbers in one or more genomes wherein repetitive sequences that bind to multiple loci in a reference chromosome spread are either substantially removed and/or their hybridization signals suppressed. The invention termed Comparative Genomic Hybridization (CGH) provides for methods of determining the relative number of copies of nucleic acid sequences in one or more subject genomes or portions thereof (for example, a tumor cell) as a function of the location of those sequences in a reference genome (for example, a normal human genome). The intensity(ies) of the signals from each labeled subject nucleic acid and/or the differences in the ratios between different signals from the labeled subject nucleic acid sequences are compared to determine the relative copy numbers of the nucleic acid sequences in the one or more subject genomes as a function of position along the reference chromosome spread. Amplifications, duplications and/or deletions in the subject genome(s) can be detected. Also provided is a method of determining the absolute copy numbers of substantially all RNA or DNA sequences in subject cell(s) or cell population(s).
摘要翻译：公开了包括使用原位杂交来检测一个或多个基因组中的异常核酸序列拷贝数的新方法，其中结合参考染色体扩增的多个基因座的重复序列基本上被去除和/或其杂交信号被抑制。称为比较基因组杂交（CGH）的发明提供了确定一个或多个受试者基因组或其部分（例如肿瘤细胞）中核酸序列的相对拷贝数的方法，作为这些序列的位置的函数参考基因组（例如，正常人类基因组）。比较来自每个标记的对象核酸的信号的强度和/或来自标记的目标核酸序列的不同信号之间的比率差异，以确定一个或多个核酸序列中核酸序列的相对拷贝数主题基因组作为沿着参考染色体扩散的位置的函数。可以检测主题基因组中的扩增，重复和/或缺失。还提供了确定受试细胞或细胞群体中基本上所有RNA或DNA序列的绝对拷贝数的方法。

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