Copy number alterations and allelic ratio in relation to recurrence of rectal cancer

Background

In rectal cancer, total mesorectal excision surgery combined with preoperative (chemo)radiotherapy reduces local recurrence rates but does not improve overall patient survival, a result that may be due to the harmful side effects and/or co-morbidity of preoperative treatment. New biomarkers are needed to facilitate identification of rectal cancer patients at high risk for local recurrent disease. This would allow for preoperative (chemo)radiotherapy to be restricted to high-risk patients, thereby reducing overtreatment and allowing personalized treatment protocols. We analyzed genome-wide DNA copy number (CN) and allelic alterations in 112 tumors from preoperatively untreated rectal cancer patients. Sixty-six patients with local and/or distant recurrent disease were compared to matched controls without recurrence. Results were validated in a second cohort of tumors from 95 matched rectal cancer patients. Additionally, we performed a meta-analysis that included 42 studies reporting on CN alterations in colorectal cancer and compared results to our own data.

Results

The genomic profiles in our study were comparable to other rectal cancer studies. Results of the meta-analysis supported the hypothesis that colon cancer and rectal cancer may be distinct disease entities. In our discovery patient study cohort, allelic retention of chromosome 7 was significantly associated with local recurrent disease. Data from the validation cohort were supportive, albeit not statistically significant, of this finding.

Conclusions

We showed that retention of heterozygosity on chromosome 7 may be associated with local recurrence in rectal cancer. Further research is warranted to elucidate the mechanisms and effect of retention of chromosome 7 on the development of local recurrent disease in rectal cancer.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1550-0) contains supplementary material, which is available to authorized users.     

Lipid content and fatty acid consumption in zoospores/developing gametophytes of Saccharina latissima (Laminariales, Phaeophyceae) as potential precursors for secondary metabolites as phlorotannins

Phlorotannins are considered inter alia to act protective to a variety of stressors, while lipids in spores are known to fuel various metabolic processes during spore release and settlement. Here, phlorotannin production in zoospores/juvenile gametophytes in relation to lipid metabolism was investigated for the first time in order to study-related metabolic costs. The experiment was carried out in Ny-?lesund (Svalbard, Arctic) within the development from spores to juvenile gametophytes of the brown alga Saccharina latissima over 20 days. In the release stage, the total phlorotannin content of single zoospores was 1.5 × 10⁻⁷ μg and 1.9 × 10⁻⁷ μg in the surrounding medium. Upon release, the total amount of lipids was 1.76 × 10⁻⁵ μg lipid zoospore⁻¹ containing the major fatty acids 16:0 and 18:0, 18:1(n-9), 18:2 (n-6), 18:3(n-3), 20:4(n-6), and 20:5(n-3). During development from spores to gametophytes, a decrease in fatty acids was observed via electron microscopy and a decrease in the fatty acid 18:1(n-9) from 45 to 30% was measured by gas chromatography in particular. While phlorotannin content within the spores remained stable, phlorotannins accumulated in the surrounding medium of gametophytes to 4.0 × 10⁻⁷ μg phlorotannins spore⁻¹ indicating exudation processes. Results obtained support the key and multifunctional role of lipids in zoospore/gametophyte metabolism and may indicate that gametophytes of S. latissima need approximately 10 days to switch to photo-autotrophic strategies, becoming independent of storage lipids. In addition, fatty acids might represent an essential energy source to fuel adaptive responses.     

Photosynthetic light requirements and vertical distribution of macroalgae in newly ice-free areas in Potter Cove,South Shetland Islands,Antarctica

In Potter Cove, Antarctica, newly ice-free areas appeared due to glacial retreat. Simultaneously, the inflow of sediment increased, reducing underwater photosynthetically active radiation (PAR, 400–700 nm). The aim of this study was to determine the photosynthetic characteristics of two macroalgal species colonizing three newly ice-free areas, A1, A2 and A3, with increasing degree of glacial influence from A1 to A3. Turbidity, salinity and temperature were measured, and light attenuation coefficients (K _d) calculated and considered as a proxy for glacial sediment input. The lower depth distribution of the red alga Palmaria decipiens and the brown alga Himantothallus grandifolius was 10 m in A3, 20 m in A2 and 30 m in A1. Both species were then collected, at 5 and 10 m at all areas. Photosynthetic parameters and the daily metabolic carbon balance (CB) were determined. K _d was significantly higher in A3 compared with A1 and A2. The CB of P. decipiens was significantly higher in A1 followed by A2 and A3, and significantly higher at shallower than at greater depth. For H. grandifolius CB was significantly lower in A3 and in A2 at deeper depths compared with the rest of areas and depths. The lower distribution limit of the algae was positively correlated to the light penetration. An increase in the sediment run-off due to global warming might lead to an elevation of the lower depth distribution limit but retreating glaciers can open new space for macroalgal colonization. These changes will probably affect macroalgal primary productivity in Potter Cove with consequences for the coastal ecosystem.     

Life strategy, ecophysiology and ecology of seaweeds in polar waters

Polar seaweeds are strongly adapted to the low temperatures of their environment, Antarctic species more strongly than Arctic species due to the longer cold water history of the Antarctic region. By reason of the strong isolation of the Southern Ocean the Antarctic marine flora is characterized by a high degree of endemism, whereas in the Arctic only few endemic species have been found so far. All polar species are strongly shade adapted and their phenology is finely tuned to the strong seasonal changes of the light conditions. The paper summarises the present knowledge of seaweeds from both polar regions with regard to the following topics: the history of seaweed research in polar regions; the environment of seaweeds in polar waters; biodiversity, biogeographical relationships and vertical distribution of Arctic and Antarctic seaweeds; life histories and physiological thallus anatomy; temperature demands and geographical distribution; light demands and depth zonation; the effect of salinity, temperature and desiccation on supra-and eulittoral seaweeds; seasonality of reproduction and the physiological characteristics of microscopic developmental stages; seasonal growth and photosynthesis; elemental and nutritional contents and chemical and physical defences against herbivory. We present evidence to show that specific characteristics and adaptations in polar seaweeds help to explain their ecological success under environmentally extreme conditions. In conclusion, as a perspective and guide for future research we draw attention to many remaining gaps in knowledge. Dedicated to Prof. Dr. Gunter O. Kirst and to Prof. Dr. Klaus Lüning on occasion of their retirement 28. Februar 2006 and 31. March 2006, respectively.     

Human lymphocytes exposed to low doses of ionizing radiations become refractory to high doses of radiation as well as to chemical mutagens that induce double-strand breaks in DNA

Human lymphocytes exposed to low doses of ionizing radiation from incorporated tritiated thymidine or from X-rays become less susceptible to the induction of chromatid breaks by high doses of X-rays. This response can be induced by 0.01 Gy (1 rad) of X-rays, and has been attributed to the induction of a repair mechanism that causes the restitution of X-ray-induced chromosome breaks. Because the major lesions responsible for the induction of chromosome breakage are double-strand breaks in DNA, attempts have been made to see if the repair mechanism can affect various types of clastogenic lesions induced in DNA by chemical mutagens and carcinogens. When cells exposed to 0.01 Gy of X-rays or to low doses of tritiated thymidine were subsequently challenged with high doses of tritiated thymidine or bleomycin, which can induce double-strand breaks in DNA, or mitomycin C, which can induce cross-links in DNA, approximately half as many chromatid breaks were induced as expected. When, on the other hand, the cells were challenged with the alkylating agent methyl methanesulfonate (MMS), which can produce single-strand breaks in DNA, approximately twice as much damage was found as was induced by MMS alone. The results indicate that prior exposure to 0.01 Gy of X-rays reduces the number of chromosome breaks induced by double-strand breaks, and perhaps even by cross-links, in DNA, but has the opposite effect on breaks induced by the alkylating agent MMS. The results also show that the induced repair mechanism is different from that observed in the adaptive response that follows exposure to low doses of alkylating agents.     

3-Aminobenzamide does not affect X-ray-induced cytogenetic damage in G0 human lymphocytes

The inhibition of poly(ADP-ribose) polymerase by 3-aminobenzamide (3AB) has been reported to have very different effects on X-ray-induced chromosome aberrations in G0 human lymphocytes. One group of investigators observed a 2-3-fold increase in the yield of rings, dicentrics and chromosome breaks after X-irradiation and 3AB treatment, whereas another group found that 3AB had no effect on X-ray-induced chromosome aberrations. To resolve this discrepancy, we repeated the experiments as described by both groups and found no effect of 3 mM or 5 mM 3AB on the frequency of chromosome aberrations induced by either 1 Gy or 2 Gy of X-rays. Furthermore, we found no effect of 3AB on X-ray-induced aberration yields in C-banded prematurely condensed chromosome preparations from unstimulated human lymphocytes. These results indicate that poly(ADP-ribose) polymerase is not involved in the repair of cytogenetic damage in G0 human lymphocytes.     

PHOTOINHIBITION AND RECOVERY AFTER HIGH LIGHT STRESS IN DIFFERENT DEVELOPMENTAL AND LIFE-HISTORY STAGES OF LAMINARIA SACCHARINA (PHAEOPHYTA)1,2

The capacity to cope with high light stress was investigated in different life-history and developmental stages of Laminaria saccharina Lamour. sporophytes and gametophytes. Changes in photosynthetic efficiency and in the level of photoinhibition were measured by in vivo fluorescence changes of photosystem II. Pigment content was studied using high performance liquid chromatography. Additionally, the morphology of the various developmental stages during the life cycle was studied by light microscopy in relation to the photosynthetic parameters. High light stress (2 h, 500 μmol.m-².s^?1) induced photoinhibition of photosynthesis with fast kinetics in older sporophytes and gametophytes. In contrast, the absolute degree of photoinhibition after light stress was higher in younger than in older sporophytes. Photosynthesis recovered faster in older sporophytes and gametophytes compared to young sporophytes. In very young sporophytes, photosynthesis did not recover fully even after 12 h exposure to low light, indicating severe photodamage. Kinetics of recovery in old sporophytes and in gametophytes showed a fast and a slow phase, whereas younger sporophytes recovered only with a slow phase, The fast phase is indicative of a decline of the photoprotective process, whereas the slow phase indicates a recovery from photodamage. The capacity to cope with high light stress in Laminaria sporophytes increased with increasing age of the thalli. The gametophytes are less sensitive to high light stress and may be selected to endure unfavorable white light conditions. Investigation of the xanthophylls showed that the higher resistance to high light is not caused solely by a higher content of xanthophyll cycle pigments. Additionally, changes in the thallus structure during the development of the sporophytes seemed to cause a higher resistance to high light. The observed changes in the ability to cope with high light in the different life-history and developmental stages of Laminaria saccharina may influence the distribution of the species on the shore.     

TEMPERATURE REQUIREMENTS FOR GROWTH AND SURVIVAL OF ANTARCTIC RHODOPHYTA1

The temperature requirement for growth and the upper survival temperatures (USTs) of 15 Antarctic red algal species collected on King George Island (South Shetland Islands) and Signy Island (South Orkney Islands) were determined. Two groups with different temperature requirements were identified. 1) A “eurythermal” group includes Rhodymenia subantarctica, Phyllophora ahnfeltioides, Gymnogongrus antarcticus, and Rhodochorton purpureum, growing between 0° and 10°C with optimum values at (0°) 5°(l0°)C. The USTs of these species and of Porphyra endiviifolium, Delesseria lancifolia, and Bangia atropurpurea were between 22° and 16°C. These species survived temperatures in a similar range as most endemic Arctic or Arctic/cold-temperate species but exhibited a lower temperature demand for growth, suggesting an earlier contact with low temperatures than Arctic species. 2) A stenothermal group includes Pantoneura plocamioides, Myriogramme mangini, Ballia callitricha, Phyllophora antarctica, Gigartina skottsbergii, Georgiella confluens, and Plocamium cartilagineum growing at 0° or ≤5°C with optimum values at 0° or 5°C. The USTs of these species and of Phycodrys austrogeorgica were between 14° and 7°C. The species of this group must have had an even earlier contact with the Antarctic cold-water environment than species of the “eurythermal” group. Gigartina skottsbergii, Georgiella confluens, Plocamium cartilagineum, and Pantoneura plocamioides were probably exposed longer to low temperatures than the other species of this group or Antarctic green and brown algae because they show the lowest temperature requirements so far determined in seaweeds. The results are discussed in the context of present local temperature regimes at the localities where the isolates were collected. Moreover, an attempt was made to explain the geographic distribution of individual species by the temperature requirements determined in this study. Only a few of the distribution limits are determined by temperature growth and/or survival characteristics. In many species (Rhodymenia subantarctica, Ballia callitricha, Gigartina skottsbergii, Bangia atropurpurea, Rhodochorton purpureum, and Plocamium cartilagineum), the development of temperature ecotypes is evident.     

Stable carbon isotope composition,depth distribution and fate of macroalgae from the Antarctic Peninsula region

Summary Stable carbon isotope composition of macroalgae collected at King George Island (Antarctica) ranged from about -8 to -34. We hypothesize that the ¹³C values are related to the depth distribution: species inhabiting greater depth had much lower values (around-30) compared to species from shallower waters (around -17). Isotopic studies on sediment trap samples from the King George Basin (2,000 m deep) revealed that benthic macroalgae contributed strongly to the total organic carbon pool of the deeper basin waters during austral spring and summer. Fragments of brown macroalgae (Desmarestiales) were detected in microscopical analyses of semi-thin sections of sediment samples from the Bransfield Strait. Possible mechanisms regarding the erosion of benthic macroalgae and their transport to the deeper waters and to the sediment are summarized.