Methods and probes for the detection of cancer
a cancer and probe technology, applied in the field of methods and probes for cancer detection, can solve the problems of death in most patients, and achieve the effect of improving sensitivity
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example 1
Probe Selection
[0068] A collection of 26 probes was assembled as candidates for detecting chromosomal abnormalities in lung cancer by in situ hybridization. The probes were hybridized to a collection of lung tumor touch preparations, and the distribution of the copy number per cell of each probe target was determined. In order to conserve tumor specimens, multi-color hybridizations were utilized to limit the number of hybridization regions per specimen to 8. To achieve this, the 26 probes were labeled with several different fluorophores. Mixtures of 3 or 4 probes each were prepared from the labeled probes forming the 8 probe sets. Where possible, chromosome enumeration probes and locus specific probes that target the same chromosome were combined in the same set to distinguish whole chromosome aneuploidy from gains and losses of regions within a chromosome.
[0069] The 26 probes selected for hybridization to lung touch preparations are described in Table 1. The probes included 13 ch...
example 2
Analysis of In Situ Hybridization Data
[0090] The target copy number data for each of the normal and tumor specimens was analyzed for the ability of each probe to discriminate between tumor and normal specimens (discriminate analysis) and for the ability of probe combinations to discriminate between tumor and normal specimens (combinatorial analysis). These analyses were used as part of the data considered in deciding which probes should be used individually or in concert to best identify lung cancer cells.
Discriminate Analysis
[0091] The ability of individual probes to discriminate between the normal specimen group and the tumor specimen group was evaluated first by comparing the averages and standard deviations of the percentages of abnormal cells found in each group. These data are listed in Tables 3 (normal specimen group) and 4 (tumor specimen group). The first 26 rows in each table lists data derived from absolute target counts per cell, for each of the 26 probes tested. For...
example 3
Selection of Probe Sets
[0109] Table 13 lists probes and probe sets selected by analyzing the data from the discriminate and combinatorial analyses and applying the probe selection criteria described herein. The probe sets of Table 13 range in size from a single probe to 4 probes. Assays using additional probes, e.g., more than four, and additional fluorescent labels can be performed.
[0110] The single probes listed in Table 13 are the probes that individually showed improvement over cytology. These include LSI 5p15, LSI 7p12, LSI 8q24, CEP 1, CEP 6, and CEP 9. For each of these probes, the vector value was less than 0.400 for two of the cutoff values tested. Other probes described herein also gave vector values less than 0.400 for a single cutoff. However, good performance for two cutoff values implies that a probe is more robust.
[0111] Next, Table 13 lists 2-probe combinations. The probe pairs placed in this group were required to have a vector value less than 0.400 and rank in t...
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