Featured Research

from universities, journals, and other organizations

Genetic differences distinguish stomach cancers, treatment response

Date:
September 16, 2011
Source:
Duke University Medical Center
Summary:
Stomach cancer is actually two distinct disease variations based on its genetic makeup, and each responds differently to chemotherapy, according to an international team of scientists.

Stomach cancer is actually two distinct disease variations based on its genetic makeup, and each responds differently to chemotherapy, according to an international team of scientists led by researchers at Duke-National University of Singapore Graduate Medical School.

The finding, published in the Aug. 1, 2011, edition of the journal Gastroenterology, is the first large-scale genomic analysis of gastric cancer to confirm the two discrete tumor types.

The researchers also found that a certain regimen of chemotherapy is more effective on one tumor type, while a different drug works best on the other, setting the groundwork for a more effective approach to treating gastric cancer patients.

"Our study is the first to show that a proposed molecular classification of gastric cancer can identify genomic subtypes that respond differently to therapies, which is crucial in efforts to customize treatments for patients," said Patrick Tan, M.D., PhD, senior author of the study and associate professor in the Cancer and Stem Cell Biology Program at the Duke-NUS Graduate Medical School.

An estimated 21,000 people in the United States will be diagnosed with stomach cancer this year, and 10,570 will die of the disease, according to the National Cancer Institute. Worldwide, only lung cancer is more lethal.

Patients have long had markedly different responses to treatments, suggesting that their tumors may have underlying differences.

Hinting at those differences, a microscopic pathology test developed in the 1960s broadly described how well the tumor cells clumped together, typing them as either "intestinal" or "diffuse." Known as the Lauren classification, after the doctor who first described the distinctions, the analysis fell short as a reliable prognostic tool.

"Most gastric cancer patients today are still being treated with a common one-size-fits-all regimen," said Tan, who also serves as group leader at the Genome Institute of Singapore and a senior investigator at the Cancer Sciences Institute of Singapore.

"One reason for this is that the Lauren classification requires significant gastric cancer experience and there is considerable variation in classifying gastric cancers, even among qualified pathologists," Tan said.

But the genetic findings by the Singapore-based researchers add greater specificity to the microscopic classifications and, for the first time, provide some guidance for doctors to prescribe effective treatments.

The team first analyzed 37 gastric cancer cell lines, which were pure cancer cells free of blood, tissue and other adulterations that could skew results.

Gene expression profiles yielded highly distinct patterns that indicated the two subtypes. In 64 percent of cases, the genetic subtypes validated the Lauren classifications -- either intestinal or diffuse. In the other 36 percent of cases, the genomic process distinguished the subtypes where the pathology test could not.

Findings were confirmed using tumor samples from 521 cancer patients.

"It was quite reassuring to us that the genomic subtypes were associated with Lauren's system," Tan said. "There is a general assumption in the field that intestinal and diffuse gastric cancers (as classified by Lauren) represent two very different versions of gastric cancer, and now genomic data confirms this by demonstrating that the two genomic subtypes have very different molecular patterns."

Establishing the highly accurate definition of tumor subtypes enabled the researchers to observe the different responses to chemotherapy. The intestinal-type tumors showed significantly better response to the chemotherapies 5-fluorouracil and oxaliplatin, and were more resistant to cisplatin than the diffuse tumors.

"The exact mechanistic reasons for this difference are currently unclear, and this is an area that we are actively working on," Tan said, adding that the researchers are working to find subtype-specific molecular vulnerabilities to drugs.

The researchers have launched a prospective clinical trial, called the 3G study, where gastric cancer tumors will be genomically profiled, and treatments will be allocated on the basis of the tumor type.

In addition to Duke-NUS, research institutions included the National Cancer Centre Singapore; National University of Singapore; Singapore General Hospital; Genome Institute of Singapore; Yonsei Cancer Center, Seoul, South Korea; Peter MacCallum Cancer Centre, East Melbourne, Australia; National University Health System, Singapore; Kanagawa Cancer Center, Yokohama, Japan; Leeds Institute for Molecular Medicine, Leeds, England; Yonsei University College of Medicine, Seoul, South Korea; MD Anderson Cancer Center, Houston, Texas.

The study was funded by the Biomedical Research Council and National Medical Research Council of Singapore, Duke-NUS Graduate Medical School, and the Cancer Sciences Institute of Singapore. The researchers reported no conflicts of interest.


Story Source:

The above story is based on materials provided by Duke University Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. Iain Beehuat Tan, Tatiana Ivanova, Kiat Hon Lim, Chee Wee Ong, Niantao Deng, Julian Lee, Sze Huey Tan, Jeanie Wu, Ming Hui Lee, Chia Huey Ooi, Sun Young Rha, Wai Keong Wong, Alex Boussioutas, Khay Guan Yeoh, Jimmy So, Wei Peng Yong, Akira Tsuburaya, Heike Grabsch, Han Chong Toh, Steven Rozen, Jae Ho Cheong, Sung Hoon Noh, Wei Kiat Wan, Jaffer A. Ajani, Ju–Seog Lee, Manuel Salto Tellez, Patrick Tan. Intrinsic Subtypes of Gastric Cancer, Based on Gene Expression Pattern, Predict Survival and Respond Differently to Chemotherapy. Gastroenterology, 2011; 141 (2): 476 DOI: 10.1053/j.gastro.2011.04.042

Cite This Page:

Duke University Medical Center. "Genetic differences distinguish stomach cancers, treatment response." ScienceDaily. ScienceDaily, 16 September 2011. <www.sciencedaily.com/releases/2011/08/110801160150.htm>.
Duke University Medical Center. (2011, September 16). Genetic differences distinguish stomach cancers, treatment response. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/2011/08/110801160150.htm
Duke University Medical Center. "Genetic differences distinguish stomach cancers, treatment response." ScienceDaily. www.sciencedaily.com/releases/2011/08/110801160150.htm (accessed July 31, 2014).

Share This




More Health & Medicine News

Thursday, July 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

House Republicans Vote to Sue Obama Over Healthcare Law

House Republicans Vote to Sue Obama Over Healthcare Law

Reuters - US Online Video (July 31, 2014) The Republican-led House of Representatives votes to sue President Obama, accusing him of overstepping his executive authority in making changes to the Affordable Care Act. Mana Rabiee reports. Video provided by Reuters
Powered by NewsLook.com
Despite Health Questions, E-Cigs Are Beneficial: Study

Despite Health Questions, E-Cigs Are Beneficial: Study

Newsy (July 31, 2014) Citing 81 previous studies, new research out of London suggests the benefits of smoking e-cigarettes instead of regular ones outweighs the risks. Video provided by Newsy
Powered by NewsLook.com
Dangerous Bacteria Kills One in Florida

Dangerous Bacteria Kills One in Florida

AP (July 31, 2014) Sarasota County, Florida health officials have issued a warning against eating raw oysters and exposing open wounds to coastal and inland waters after a dangerous bacteria killed one person and made another sick. (July 31) Video provided by AP
Powered by NewsLook.com
Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



    Save/Print:
    Share:

    Free Subscriptions


    Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

    Get Social & Mobile


    Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

    Have Feedback?


    Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
    Mobile: iPhone Android Web
    Follow: Facebook Twitter Google+
    Subscribe: RSS Feeds Email Newsletters
    Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins