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Patent: Genetic Probe For Smoking-Related Cancers
Patent: Genetic Probe For Smoking-Related Cancers | hou_txbz,Ruth Katz,Jiang Feng,patent,8093001,detection,diagnosis,smoking,smoke,cancer,tobacco,

Ruth Katz and Jiang Feng, both of Houston, received U.S. Patent 8,093,001 for “Detection and diagnosis of smoking related cancers.”

Texas Business Patent Of The Day:  Two Texans devised a way to probe genes for lung and other smoking related cancers.  

Ruth Katz and Jiang Feng, both of Houston, received U.S. Patent 8,093,001 for “Detection and diagnosis of smoking related cancers.”

The two filed for the patent on April 15, 2010. 

The patent assignee is the Board of Regents, The University of Texas System in Austin.

The present invention relates to the fields of oncology, genetics and molecular biology, according to the patent document.

 More particular the invention relates to the use of two probes for regions of human chromosomes 3 and 10 that are highly predictive of the development of neoplasia and progression of neoplastic events. 

Lung cancer is one of the leading causes of cancer death in the world. The high mortality rate for lung cancer probably results, at least in part, from the lack of standard clinical procedures for the diagnosis of the disease at early and more treatable stages compared to breast, prostate, and colon cancers.

There is also extremely poor prognosis associated with diagnosis of the disease, especially in advanced disease. It is important that strategies to detect early stage lung carcinoma or its precursors, such as atypical squamous metaplasia, dysphasia and carcinoma-in-situ in subjects at high risk be devised. 

Cigarette smoking over a prolonged period of time is the most important risk factor in the development of lung and other smoking related cancers, with other risk factors including exposure to passive smoking, certain industrial substances such as arsenic, some organic chemicals, radon and asbestosis, ingestion of alcohol, radiation exposure from occupational, medical and environmental sources, air pollution and tuberculosis. Many of these factors greatly increase the risk of development of lung and other smoking related cancers if they occur in a person who is concurrently a smoker. 

Genetic detection of human disease states is a rapidly developing field.

However, some problems exist with this approach. A number of known genetic lesions merely predispose to development of specific disease states. Individuals carrying the genetic lesion may not develop the disease state, while other individuals may develop the disease state without possessing a particular genetic lesion.

In human cancers, genetic defects may potentially occur in a large number of known tumor suppresser genes and proto-oncogenes. 

 Because of the grim prognosis of lung cancer with a ten year survival rate of <5% the only curable cancers are those diagnosed in the early stages and treated surgically. There is a shift of interest towards diagnosis and study of early and preneoplastic states. Because early detection and effective chemoprevention therapy have potential to be curative, it is imperative to stratify the patients in clinical trials. These patients need to be monitored fore results of chemoprevention therapy and also for predictions whether a particular preneoplastic lesion may progress. 

The present invention provides probes located on chromosomes 3p21.3 and 10q22 useful in the diagnosis and prognosis of cancers related to smoking. In one embodiment, a method for identifying a subject at high risk for the development, recurrence, or metastasis of cancer comprising the steps of (a) obtaining a test sample from a subject; (b) providing a nucleic acid probe targeting RPL14, CD39L3, PMGM, or GC20; (c) contacting the probe with the test sample; and (d) analyzing DNA from the sample whereby aberrations in the hybridization of said probe to said DNA was compared to wild type DNA, indicating the risk for the development, recurrence, or metastasis of cancers. 

More specifically the method identifies the risk for the development of cancers. The cancer may be lung, upper airway primary or secondary, head or neck, bladder, kidneys, pancreas, mouth, throat, pharynx, larynx, esophagus, brain, liver, spleen, kidney, lymph node, small intestine, pancreas, blood cells, colon, stomach, breast, endometrium, prostate, testicle, ovary, skin, bone marrow and blood cancer. In preferred embodiments, the cancer is lung cancer. The test sample can include, but is not limited to, a surgical or biopsy specimen, paraffin embedded tissue, frozen tissue, surgical fine needle aspirations, bronchial brushes, bronchial washes, bronchial lavages, buccal smears, sputa, peripheral blood lymphocytes, esophageal brush, a fine needle aspiration, urinary specimens such as bladder washings and voided urine, and esophageal washes. 

In one embodiment, it is provided that the subject can come from a group comprising smokers, former smokers, or non-smokers. In a similar embodiment, the test sample comes from said subject who has not previously been diagnosed with cancer. 

It is a further embodiment of this invention that additional testing, agents or treatments may be performed after the risk for the development of said cancers has been analyzed. This includes, but is not limited to, a spiral CT-scan, cancer therapies and pharmaceutical treatments which can include radiotherapeutic agents, surgical treatment for removal of the cancerous growth, chemotherapeutic agents, antibiotics, alkylating agents and antioxidants, biological modifying respidase drugs and other agents. These agents and treatments can be used alone or in combination with other agents. 

In certain embodiments, it is contemplated that FISH is used to measure the aberrations in the particular loci. A unique 3p21.3 probe can be from 1000 to 2000 base pairs or larger and used for detection in a region of about 180,000 base pairs. The probe can be labeled with a fluorophore, or more specifically digoxigenin. A specific 10q22 probe can be used in conjunction with the 3p21 probe. In certain embodiments, a control probe is used which can be labeled with a fluorophore, or more specifically spectrum orange. The control probe is a chromosome 3 stable marker or more specifically Centromere 3 (CEP 3). 

In another embodiment, there is provided a method for identifying a subject at high risk for the development, recurrence, or metastasis of cancer comprising: (a) obtaining a lung test sample from a subject; (b) providing a specific10q22 DNA probe; (c) contacting said probe with said test sample; and (d) analyzing DNA from said test sample, whereby aberrations in the hybridization of said probe to said DNA is compared to wild type DNA, indicating the risk for the development, recurrence or metastasis of said cancers. More specifically the method identifies the risk of the recurrence or metastasis of cancers. In a further embodiment, the probe size is from 1000 to 2000 base pairs or larger, for detection in a region of about 200,000 base pairs. In an additional embodiment, a specific 3p21 probe can be used with the 10q22 DNA probe. The control probe is a chromosome 10 stable marker, or more specifically Centromere10 (CEP10). 

In another embodiment, there is provided a method for predicting the progression or metastasis of non-small cell carcinoma and other carcinoma in a subject comprising: (a) obtaining a test sample from a subject; (b) providing a RPL14, CD39L3, PMGM, or GC20 gene probe; (c) contacting said probe with said test sample; and (d) analyzing DNA from said test sample. 

In yet another embodiment, there is provided a method for predicting the progression or metastasis of non-small cell carcinoma in a subject comprising: (a) obtaining a lung test sample from a subject; (b) providing a specific10q22 DNA probe; (c) contacting said probe with said test sample; and (d) analyzing DNA from said test sample. 

In a further embodiment, there is provided a method for the staging lung of cancer in a subject comprising determining the deletion distribution of the 3p21.3 region. 

In one embodiment, there is provided a method of determining likelihood of relapse or a new primary for a cancer subject comprising determining genetic aberrations at chromosomal loci 3p21.3 or 10q22 in DNA of bronchial tissue adjacent to tumor tissue from said subject, wherein abnormalities in DNA of said adjacent tissue correlate with relapse of said cancer. The cancer can comprise lung cancer or more specifically non-small cell carcinoma, adenocarcinoma, or squamous cell carcinoma. A specific gene probe may comprise RPL 14, CD39L3, PMGM, or GC20, or a 10q22 DNA probe. The 10q22 probe lies adjacent to the PTEN gene which is frequently involved non-small cell cancer. Both the 3p and the 10q probe can be used simultaneously. The test sample can be chosen from the same or contralateral lung, and can consist of tumorous or nontumorous bronchial cells. 

In yet another embodiment, there is provided a method of identifying an individual to be segregated from a high risk environment comprising: (a) obtaining a test sample from a subject; (b) providing a gene probe containing RPL14, CD39L3, PMGM, and GC20 genes and PTEN or a 10q22 DNA probe, (c) contacting said probe with said test sample; and (d) analyzing DNA from said test sample, whereby said analysis is used to identify an individual who is highly susceptible to the development of lung cancer and who should not be exposed to a high risk environment.